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Coi^iTis 50 

The  Acid  Autointoxications  50 

Sawne  Therapy  -        -       -       -  75 

Drink  Restriction         -       -  75 

Diabetes  Mei^wtus      -       -       -  1.50 
Inanition  and  Fattening  Cures  1.50 

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NEW   ASPECTS 
OF   DIABETES 

PATHOLOGY  AND  TREATMENT 


BY 

PROF.  DR.  CARL  VON  NOORDEN 

Professor  of  the  First  Medical  Clinic^  Vienna 


Lectures  Delivered  at  the  New  York  Post-Graduate 
Medical  School    and  Published  by  their  Authority 


NEW  YORK 

E.  B.  TREAT  &  COMPANY 

1913 


Copyright,  1912 

By  E.  B.  Treat  &  Company 

All  Rights  Reserved 


h 'i 


LIDRAR 


PREFATORY  NOTE 

One  of  the  leading  features  of  internal  medicine, 
as  taught  and  practiced  in  Germany  at  the  present 
time,  is  the  attention  given  to  problems  of  digestion 
and  metabolism.  The  advances  in  theoretical  chem- 
istry and  their  application  to  the  studies  in  the  phy- 
siology and  pathology  of  nutrition  have  opened  up 
most  promising  perspectives  into  the  correlations  of 
organs  of  the  human  body  and  have  furthermore  stim- 
ulated in  Germany,  in  a  most  fruitful  way,  that  art 
of  healing  which  is  based  on  scientific  principles. 

Our  country  has  followed  Germany  very  closely  in 
the  last  ten  years  in  this  direction  and  indeed  has 
taken  an  advanced  independent  attitude  on  many  fun- 
damental points.  The  general  interest  in  these  mat- 
ters is  shown  by  the  valuable  researches  made  upon 
foods  which  the  Department  of  Agriculture  of  our 
government  has  carried  out  and  by  the  interest  demon- 
strated by  our  universities,  scientific  laboratories  and 
the  general  public.  The  medical  profession  in  gen- 
eral practice,  however,  has  not  as  yet  taken  that  in- 
terest in  questions  of  nutrition  which  these  problems 
deserve,  but  the  interest  is  growing  rapidly  and  the 
demands  for  teaching  on  these  lines  has  been  felt  more 
and  more  in  medical  colleges  and  especially  in  post- 
graduate medical  schools. 

Prof.   Carl  von  Noorden  has  been   identified   for 


304746 


PREFATORY   NOTE 

more  than  twenty  years  with  the  progress  of  the  theo- 
retical and  applied  knowledge  of  metabolism  and  is 
known  to  the  American  as  well  as  to  the  European 
physician.  It  is  therefore  a  source  of  great  pleasure 
to  the  board  of  directors  and  to  the  faculty  of  the 
New  York  Post-Graduate  Medical  School  to  have  had 
him  deliver  a  series  of  lectures  on  such  problems  be- 
fore the  matriculates  and  guests  of  their  school.  This 
publication  covers  those  lectures  delivered  in  October, 
1912. 

It  will  be  highly  appreciated,  we  are  sure,  that  these 
lectures  have  become  available  in  this  form  to  the 
progressive  student  of  medicine  in  our  country. 

LuDWiG  Kast. 

New  York  City, 
November  i,  1912. 


CONTENTS 

CHAPTER  PAGE 

INTRODUCTION ii 

I.    THE   SOURCE   OF   SUGAR 13 

A.  Carbohydrates 13 

B.  Proteins 14 

a.  The    Carbohydrate    Group    of    the    Albumin 

Molecule 14 

b.  The   Aminoacids 15 

c.  Influence    of    Various    Proteins 16 

d.  The  Specific  Dynamic  Influence  of  Proteins   .  19 

e.  The  Quotient  D  ^  N 22 

C.  Fats 25 

a.  The   Circulation   of   Fat 25 

b.  Does   Muscle  Tissue  Oxidize  Fats?  ....  28 

c.  Limits  of  Sugar  Formation  from  Fat   ...  30 

d.  Decomposition  of  Fat  and  Acetone  Bodies    .  32 

e.  Arguments  for  and  against  the  Formation  of 

Sugar   from   Fat 33 

D.  Summary 38 

II.    THE  RISE  IN  CALORIC  PRODUCTION  AND  ITS 

CAUSES 40 

TIL    THE  CONTROL  OF  SUGAR  FORMATION  AND 
ITS       DISTURBANCES.       THEORY 

OF  DIABETES 45 

A.  The  Liver  as  the  Place  of  Control  ....  45 

B.  The  Influence  of  Other  Organs  on  the  Liver  49 

a.  The    Pancreas '    ....  49 

b.  The    Chromaffin    System' Si 

c.  The   Nervous   System.     Neurogenous  Diabetes  54 

d.  The    Thyroid    System 59 

e.  Diagram'    Illustrating    the    Regulation    ...  60 

C.  The    Diabetic    H'yperirritation    of    the    Sugar- 

Forming  Apparatus 64 

D.  Is   Diabetes   a   Single  Morbid  Entity?    ...  68 


CONTENTS 
CHAPTER  PAGE 

IV.    THERAPY   OF   DIABETES 7i 

A.  Introduction 73 

B.  What  Is  the  Object  of  Carbohydrate  Restric- 

tion?         74 

a.  Avoidance  of  Loss  of  Energy 74 

b.  Prevention  of  Complications 76 

c    Treatment  of  the  Hyperirritation  of  the  Sugar- 
Forming   Apparatus 81 

1.  Disadvantages    of    Carbohydrates     ...  81 

2.  Disadvantages  of  Large  Intakes  of  Albumin  85 

3.  Recovery  of  the  Sugar-Forming  Apparatus  86 

C.  Principles  of  Treatment  in  Slight  Cases   .     .  89 

D.  Principles  of  Treatment  in  Transitional  Cases  91 

E.  Principles  of  Treatment  in  Severe  Cases   .     .  92 

F.  Tolerance  Determination 95 

G.  Carbohydrates  or  Oatmeal  Cures   ......  100 

H.    Therapy    of    Acidosis no 

I.    Drugs 117 

a.  Salicylates,  Antipyrin,  Nervina,  etc 117 

b.  Mineral   Waters    . 119 

c.  Specialties,  Secret  Medicines 121 

J.    Concluding    Remarks 123 

ACETONURIA,   ITS   INFLUENCE  ON  THE  TREAT- 
MENT OF  DIABETES  MELLITUS  .  126 

A.  Slight    Glycosuria 132 

a.  Cases  in  which  Carbohydrates  had  been  freely 

used    ...     .1 133 

b.  Cases  in  which  Carbohydrates  had  been  disused  136 

B.  Severe  Forms  of  Glycosuria 140 

a.  Serai-Severe  Cases 141 

b.  The  really  Severe  Forms  of  Glycosuria   .     .  150 
C    Special  Indications 153 

a.  Alkaline    Therapy I53 

b.  Feeding        .   ^ 158 


New  Aspects  of  Diabetes 


INTRODUCTION 

Some  years  ago,  I  had  the  honor  to  deliver  here  in 
New  York  some  lectures  on  the  pathological  chemistry 
and  treatment  of  diabetes  mellitus.  I  intend  to  speak 
once  more  upon  the  same  subjects,  since  it  has  been 
represented  to  me  that  by  so  doing  I  should  be  meeting 
the  wishes  of  a  number  of  physicians  in  this  country, 
especially  as  diabetes  is  such  a  many-sided  and  vast 
field,  that  a  couple  of  lectures  given  in  1905  can 
scarcely  be  deemed  sufficient  to  cover  the  whole  ground. 
I  must,  however,  limit  myself  to  a  few  of  the  more 
interesting  questions  of  pathological  chemistry  and  to 
some  of  the  aspects  of  the  therapy  of  the  disease. 
That  which  several  years  ago  could  lay  claim  to  being 
new,  interesting  and  at  the  same  time  of  practical  im- 
portance is  already  a  part  of  the  general  medical  knowl- 
edge. It  is  not  necessary  for  me  to  repeat  to  a  learned 
circle  of  experienced  practitioners  the  elementary 
principles  of  diabetes.  However  during  the  last  years 
many  new  questions  concerning  diabetes  have  been 
worked  out ;  some,  which  seven  years  ago  were  of  pass- 
ing interest,  have  to-day  entered  into  the  arena  of 
theoretical  importance  and  are  becoming  day  by  day 
more  valuable  for  the  practical  physician.     Many  of 


12  JNTROPUCTION 

the  advances  in  the  knowledge  of  the  disease  made  dur- 
ing recent  years  have  been  carried  out  in  my  cHnic  and 
my  own  personal  experience  during  the  last  seven  years 
has  consisted  of  a  study  of  the  course  of  treatment  of 
more  than  2000  cases  of  diabetes  mellitus  in  my  clinic 
and  sanatorium.  This  extension  of  personal  investiga- 
tions together  with  the  certainty  of  some  of  the  results 
and  the  general  progress  made  in  all  countries  in  a  sci- 
entific study  of  this  condition  warrants  me  once  again 
in  addressing  you  upon  diabetes. 

We  may  turn  first  to  some  theoretical  questions. 
However,  I  will  restrict  the  discussion  to  those  prob- 
lems which  have  an  immediate  bearing  upon  the  treat- 
ment of  diabetes  and  which  it  is  necessary  to  under- 
stand if  the  patient  shall  be  well  treated.  Some  of 
these  matters  were  referred  to  in  my  previous  lectures, 
but  none  of  them  could  be  explained  with  such  certainty 
as  they  can  to-day,  and  in  many  of  the  most  important 
ones  the  answers  are  quite  otherwise  than  what  was 
expected  seven  years  ago. 


I.  THE  SOURCE  OF  SUGAR 
A.     Carbohydrates 

I  need  only  make  a  few  remarks  on  carbohydrates. 
We  know  that  all  pure  carbohydrates  and  the  chem- 
ically related  substances,  present  in  human  food,  play 
an  important  part  as  sources  of  sugar.  The  rarer 
types,  such  as  pentose  and  heptose,  scarcely  call  for  con- 
sideration, as  they  exert  only  a  slight  influence  on  the 
formation  of  sugar.  It  is  very  probable  that  in  healthy 
men  living  under  the  usual  conditions  of  nutrition, 
nearly  all  the  absorbed  carbohydrates  reappear  in  the 
liver  as  deposits  of  glycogen,  and  that  only  slight  traces 
immediately  pass  through  the  liver  and  reach  the  gen- 
eral circulation.  The  latter  condition  occurs  in  healthy 
men  only  when  excessive  quantities  of  sugar  are  taken 
and  after  absorption  make  too  great  demands  upon 
rapid  assimilation  and  fixation  by  the  liver.  The  sub- 
sequent overflooding  of  the  blood  with  sugar  is  a  step 
towards  the  condition  designated  "  alimentary  gly- 
cosuria." We  know  that  many  diseases  predispose  to 
alimentary  glycosuria  —  a  knowledge  that  is  of  diag- 
nostic as  well  as  of  theoretical  importance.  I  will  re- 
fer to  this  later  on. 

The  matter  is  a  different  one  when  it  concerns  the 
diabetic  patient.  One  of  the  most  important  —  per- 
haps the  predominant  —  of  the  disturbance  of  his  me- 

13 


14         DISORDERS    OF   METABOLISM    AND    NUTRITION 

tabolism,  lies  in  the  fact  that  the  hepatic  cell  is  unable 
to  fix  the  carbohydrate.  This  defective  function  varies 
largely  in  different  diabetics,  and  in  one  and  the  same 
case  is  not  always  maintained  at  the  same  level.  The 
disturbance  does  probably  not  consist  of  an  inability 
to  form  glycogen,  but  owing  to  a  tendency  to  de- 
compose the  just  formed  glycogen  too  rapidly,  so  that 
the  excess  appears  in  the  blood  as  glucose.  The  de- 
composition extends  more  rapidly  and  completely  as 
the  diabetes  progresses  and  in  the  same  degree  increases 
the  danger  of  marked  hyperglycaemia  and  glycosuria. 
The  carbohydrates  therefore  constitute  a  source  of 
sugar  for  the  diabetic  patient  as  for  the  healthy  in- 
dividual; but  the  tissues  of  the  former  have  lost  the 
power  of  storing  the  materials  in  depots  and  taking 
them  out  of  store  as  demands  arise.  Many  points  of 
interest  are  bound  up  with  this  fact,  and  I  must  put 
them  before  you  in  their  proper  relation  at  a  later 
stage. 

B.     Proteins 

The  question  concerning  the  why  and  wherefore  of 
protein  material  as  a  source  of  sugar  is  not  so  well 
developed. 

a.     The  Carbohydrate  Group  of  the  Albumin  Molecule 

That  proteins  do  yield  sugar,  however,  is  quite 
certain  and  it  is  quite  clear  that  the  majority  of  pro- 
teins contain  a  carbohydrate  group.  This  group  is 
split  off  during  digestion;  the  cleavage  occurs  during 


NEW  ASPECTS  OF  DIABETES  1$ 

the  action  of  the  pepsin-hydrochloric  acid,  for  the  so- 
called  albumose  does  not  contain  carbohydrates.  The 
separated  carbohydrate  behaves  just  the  same  as  a  na- 
tive carbohydrate.  It  is  absorbed  in  due  course  and 
is  carried  to  the  liver.  It  is  a  remarkable  fact  that 
certain  albumins  v^hich  are  particularly  rich  in  car- 
bohydrate groups,  e.  g.  egg  albumins,  do  not  especially 
affect  the  sugar  formation;  the  influence  is  relatively 
large  when  the  albumin  is  taken  raw  but  very  slight 
when  it  is  first  coagulated  by  heat.  On  the  other  hand, 
some  proteins  act  as  marked  excitants  of  the  sugar 
production,  such  as  muscle  albumin  (which  contains 
very  little  carbohydrate),  and  casein,  which  hardly  con- 
tains any  carbohydrate. 

The  first  question  we  may  ask  is  this:  How  is  it, 
that  the  carbohydrate  group  of  the  albumin  does  not 
excite  the  sugar  production  so  much  as  does  the  native 
carbohydrate  ?  The  answer  lies  near  at  hand ;  all  na- 
tive carbohydrates  are  absorbed  quickly  and  so  pass 
rapidly  in  large  quantities  into  the  liver.  On  the 
other  hand,  the  digestion  of  the  protein  and  the  separa- 
tion of  its  carbohydrate  group  requires  time  and  ab- 
sorption is  slow,  therefore  the  amount  of  carbohydrate 
entering  the  liver  at  the  same  time,  is  only  small,  and 
does  not,  under  ordinary  conditions,  call  for  more  than 
a  slight  display  of  energy. 

b.  The  'Aminoacids 

The  second  constituent  of  the  protein  molecule  which 
exerts  a  doubtless  influence  upon  the  sugar  formation 


l6         DISORDERS   OF   METABOLISM    AND    NUTRITION 

is  the  aminoacid  group;  this  makes  up  about  40  per 
cent,  of  the  total  protein  molecule.  If  a  diabetic  pa- 
tient, or  a  depancreatized  dog,  or  a  dog  in  which  a 
maximum  phloridzin  diabetes  is  induced,  be  fed  upon 
aminoacids,  the  glycosuria  increases.  The  matter  is 
most  clear  in  connection  with  phloridzin  diabetes. 
Equal  quantities  of  nitrogen  cause  an  identical  increase 
in  the  glycosuria,  whether  isolated  aminoacids  such 
as  alanin  or  original  protein  be  employed.  We  have 
acquired  this  knowledge  through  the  careful,  laborious 
and  painstaking  investigations  of  your  own  country- 
man, Graham  Lusk.  Although  it  does  not  follow,  that 
the  aminoacids  are  definite  and  direct  sources  of 
sugar,  the  same  result  ought  to  follow,  if  these  sub- 
stances in  ever  the  same  proportion  incite  the  forma- 
tion of  sugar,  although  they  themselves  are  not  the 
material  out  of  which  the  sugar  is  built  up.  I  am  of 
the  opinion  that  we  to-day  have  no  definite  certainty 
that  the  aminoacids  must  be  regarded  as  primary  and 
consistent  sugar  formers,  and  I  believe  that  one  would 
stop  further  progress  if  we  neglected  certain  difficulties, 
which  arise  on  our  way  towards  clearing  these  ques- 
tions. 

c.  The  Influence  of  Various  Proteins 

One  of  our  difficulties  is  the  extraordinary  differ- 
ences manifested  by  diabetics  to  vegetable  and  animal 
albumins.  If  in  a  case  of  severe  diabetes  we  order  a 
dietary  which  is  poor  in  carbohydrates  and  of  low  al- 
bumin content,  and  at  the  same  time  suffices  to  exclude 


NEW  ASPECTS  OF  DIABETES 


/ 


17 


glycosuria,  to  which  we  then  add  100  grams  of  vege- 
table albumin,  such  as  that  useful  preparation,  glidin 
(Klopfer)  the  urine  remains  free  from  sugar,  or  al- 
most so.  If,  however,  we  add  a  similar  quantity  of 
a  meat  albumin  instead  of  a  vegetable  one,  then  a 
marked  glycosuria  appears  and  persists  even  after  the 
meat  albumin  has  been  stopped. 

The  following  table  furnishes  an  example : 


Additional 

Sugar 

Day                  Food 

Food 

in  24  hours. 

I    100  g  meat,  5  eggs,  4 

yolk  of  eggs.— 

■300  g 

thick    cream.  — 

-  green 

vegetables.  —  Gluten- 

bread.—  Butter. 

— 

0 

2 

— 

0 

3 

— 

0 

4 

100  g  Glidin 

0 

5 

« 

0 

6 

1* 

0 

7 

400  g  Beef    (raw 

weight) 

5.6g. 

8 

u 

20.8 

9 

tt 

26.7 

10 

0 

7.2 

II 

0 

2.2 

12 

0 

0 

I  chose  this  example  because  it  shows  the  point 
extremely  well.  I  could  mention  some  dozen  of 
others,  however,  which  would  mirror  the  result.  Not 
all  cases  of  diabetes,  however,  serve  to  demonstrate 
this  fact.  In  the  slighter  forms,  the  influence  of  meat 
albumins  is  not  great  and  it  is  difficult  to  demonstrate 
the  reaction  of  the  patient  to  different  forms  of  al- 


1 8         DISORDERS   OF   METABOLISM    AND   NUTRITION 

bumin.  It  may  be  necessary  to  add  more  albumin 
than  the  patient  can  actually  take  before  the  glycosuria 
indication  is  reached.  On  the  other  hand,  it  is  not  al- 
ways possible  to  obtain  such  results  in  severe  cases; 
these  patients  are  most  susceptible  to  a  large  quantity 
of  albumin.  Once  a  medium  amount  of  albumin  is 
exceeded,  say  70-80  grams,  the  glycosuria  increases, 
no  matter  what  the  type  of  albumin  is.  The  most 
favorable  cases  are  those  —  as  I  have  already  men- 
tioned—  which  are  just  under  the  borderHne  of 
"  severe  diabetes.'*  For  these,  my  experience  has  led 
me  to  formulate  my  views  in  the  following  manner : — 

Meat  is  dealt  with  least  well ;  namely,  the  glycosuria 
increases  to  the  greatest  extent. 

Next  comes  casein. 

Then  follows  egg  albumin. 

Finally,  there  is  vegetable  albumin;  of  this  type 
glidin  gives  the  best  results. 

As  it  appeared  possible  that  the  unfavorable  in- 
fluence of  meat  might  be  due  to  the  presence  of  "  ex- 
tractives," we  investigated  the  effect  of  meat  which 
had  been  cooked  so  that  all  its  extractives  had  passed 
into  the  water  in  which  it  was  prepared.  We  also 
tried  fish  foods.  It  is  known  that  the  flesh  of  large 
and  old  fish  is  poorer  in  extractives  than  that  of 
mammals;  in  young  and  small  fish  the  differences  are 
not  so  marked.  As  you  know,  fish  has  long  been 
recognized  as  being  specially  useful  to  diabetics.  Our 
clinical  experience  has  shown  that  meat  and  fish,  de- 
prived of  extractives  by  artificial  means,  or  originally 


NEW   ASPECTS   OF   DIABETES  1 9 

poor  in  extractives,  induce  a  little  less  output  of  sugar 
than  extractive-rich  foods  prepared  in  the  usual  way. 
The  differences  are  not  great,  however,  except  in  the 
case  of  raw  meats.  We  must  admit  that  the  extract- 
ives do  exert  some  slight  influence  on  the  sugar  out- 
put, but  the  extent  is  not  sufficient  to  account  for  the 
differences  on  the  effect  of  animal  and  vegetable 
proteins. 

When  we  extend  the  inquiry  further,  we  are  not 
yet  able  to  speak  definitely  as  to  the  effect  of  the  vary- 
ing quantities  of  aminoacids  in  the  animal  and  vege- 
table albumins.  Here  most  probably  the  type  of  the 
aminoacids  comes  into  play,  for  each  variety  of  pro- 
tein has  its  own  quota  of  specific  aminoacids.  I  be- 
lieve that  this  opens  a  field  for  numerous  and  important 
investigations,  whose  results  will  be  of  great  benefit  in 
the  treatment  of  diabetes. 

d.  The  Specific  Dynamic  Influence  of  Proteins 

For  the  moment  I  may  advance  the  proposition  that 
the  influence  of  the  protein  molecule  upon  glycosuria 
does  not  depend  only  upon  the  fact  that  it  contains 
certain  atomic  groups  which  may  be  utilized  for  the 
formation  of  sugar,  but  that  certain  fundaments  of 
protein,  or  in  other  words,  certain  peptides  or  poly- 
peptides, act  upon  the  liver  as  powerful  inciters  to  the 
formation  of  sugar.  I  refer  here  to  an  excitant  or 
irritant  that  is  related  to,  or,  perhaps  identical  with  the 
factor  which  M.  Rubner  some  time  ago  designated  as 
the  specific  dynamic  influence  of  an  excessive  protein 


20         DISORDERS   OF   METABOLISM    AND   NUTRITION 

dietary.  Of  course,  to  this  can  be  opposed  that  in- 
creased glycosuria  may  follow  the  intake  of  a  quantity 
of  albumin  far  too  small  to  be  called  excessive.  This 
objection  cannot  be  sustained,  for  Rubner's  figures 
were  derived  from  observations  upon  healthy  men  and 
animals.  In  severe  diabetes,  we  have  to  do  with  sick 
men,  in  whom  the  energy  exchange  is  raised,  as  earlier 
writers  supposed  and  as  the  interesting  works  of  Bene- 
dict, Falta  and  Joslin  have  confirmed.  We  may  as- 
sume that  the  factors  responsible  for  the  control  of  the 
energy  exchange  are  more  liable  in  the  case  of  diabetics 
than  in  healthy  men,  so  that  influences  which  are  too 
slight  to  occasion  any  caloric  production  in  normal  in- 
dividuals exert  an  effect  upon  those  suffering  from 
diabetes.  Such  an  occurrence  is  not  an  isolated  one. 
It  is  the  same  in  fever  and  in  Basedow's  disease.  We 
know  that  the  general  caloric  production  is  increased 
in  these  conditions  and  it  is  an  old  observation  that 
large  quantities  of  albumin,  and  especially  meat  al- 
bumin, are  badly  borne  at  such  times;  in  fever  the 
temperature  goes  up  and  the  pulse  becomes  more 
rapid,  while  the  general  disturbances  such  as  headache, 
etc.,  are  more  pronounced;  in  Basedow's  disease  the 
sense  of  heat  and  the  formation  of  sweat  is  more 
marked,  the  heart  is  more  excited  and  the  tremors  in- 
crease; the  production  of  calories  is  also  apparently 
more  excessive,  for  I  have  observed  that  it  is  more 
difficult  to  obtain  a  rise  in  body  weight  when  much 
meat  is  given  than  when  the  meat  content  of  the 
dietary  is  lowered.     The  similarity  of  the  alterations 


NEW  ASPECTS  OF  DIABETES  21 

in  the  metabolism  during  fever,  Basedow's  disease  and 
diabetes  may  be  pushed  even  a  little  further.  In  all 
the  three  diseases  when  the  caloric  production  is  raised, 
hyperglycaemia  follows;  in  fact,  only  seldom  and  if 
large  quantities  of  sugar  are  given,  a  glycosuria  results, 
although  the  never  failing  hyperglycaemia  suffices  to 
show  that  in  these  three  diseases  the  qualitative  and 
quantitative  formations  of  sugar  are  disturbed  to  a 
certain  degree. 

We  have  in  these  three  diseases  a  remarkable  trio  of 
symptoms : 

1.  Raised  production  of  calories, 

2.  Hypersensibility  to  protein,  especially  meat 
protein, 

3.  Hyperglycaemia  or  glycosuria. 

These  coincidences  are  surely  more  than  accidental. 
How  are  they  connected?  We  cannot  give  a  definite 
answer,  but  we  can  approach  pretty  near  to  the  truth. 

I  take  it  for  granted  that  the  same  cause  which  in 
these  three  conditions  induces  the  endogenous  increase 
of  the  caloric  production  is  also  responsible  for  the 
irritability  of  the  sugar  forming  processes  in  the  liver. 
In  fever  and  in  Basedow's  disease  the  irritation  effect 
is  slight.  However,  hyperglycaemia  always  accom- 
panies the  raised  caloric  formation  while  with  a 
stronger  stimulus,  glycosuria  appears.  In  severe  dia- 
betes, where  the  irritability  of  the  sugar  manufacture 
is  already  intensified  through  other  causes,  the  addi- 
tional irritation  will  be  disproportionally  stronger. 

How  is  it  that  this  stimulus  follows  a  protein  in- 


22         DISORDERS   OF    METABOLISM    AND   NUTRITION 

take?  How  is  it  that  fat  does  not  induce  a  similar 
result?  I  may  here  call  to  memory  the  physiological 
fact  that  all  foods  cause  an  increased  caloric  output; 
however,  the  amount  is  most  marked  after  proteins  are 
taken.  The  oxygen  requirements  rise  to  20-25  per 
cent,  above  those  during  fasting;  the  rise  following 
the  intake  of  fat  and  carbohydrate  is  not  so  great. 
We  ascribe  the  call  for  more  oxygen  to  the  needs  of 
digestive  processes,  which  in  the  wider  sense  of  the 
term,  must  include  hepatic  processes  also.  The  energy 
put  forth  by  the  liver  during  the  assimilation  of  car- 
bohydrate is  very  slight;  with  that  of  fat  the  liver 
has  practically  nothing  to  do,  the  treatment  of  the 
absorbed  fat  being  chiefly  a  deposition  process.  It  is 
the  protein  alone  which  is  associated  with  energy  re- 
quirements and  active  work  on  the  part  of  the  liver 
and  I  regard  the  cleavage  of  the  protein  therefore  as  a 
cause  of  the  considerable  physiological  increase  of  the 
oxidation  changes  and  at  the  same  time  as  a  stimulus 
for  the  manufacture  of  sugar.  When  this  manufac- 
ture by  itself  is  abnormally  high,  as  in  diabetes,  increase 
of  the  glycosuria  results. 

e.  The  Quotient  D-~-N 

There  still  remains  for  discussion  another  im- 
portant question  of  the  relation  between  the  protein 
and  the  sugar  formation.  One  has  tried  to  learn  from 
the  metabolism  of  the  diabetic,  how  much  sugar  is 
formed  from  the  albumin.     The  question  is  an  old  one. 


NEW  ASPECTS  OF  DIABETES  23 

It  has  been  shown  long  ago  by  v.  Mering  and  Min- 
kowski in  their  experimental  pancreas  diabetes,  that  in 
diabetic  dogs  when  the  carbohydrate  stores  are  en- 
tirely used  up,  the  relation  between  the  urinary  sugar 
and  the  urinary  nitrogen  —  the  so-called  quotient  D^N 
remains  constant  whether  the  animal  is  allowed  to  fast 
or  is  fed  with  albuminous  food.  The  quotient  keeps 
very  close  to  2.8:1.  Minkowski  concluded  from  this, 
that  this  quotient  showed  the  relative  production  of 
sugar  from  albumin,  despite  the  theoretical  chemical 
calculation  that  more  sugar  could  be  yielded,  namely 
4i,  or  five  parts  of  dextrose  to  one  of  nitrogen.  The 
more  detailed  investigations  upon  phloridzin  diabetes, 
for  which  we  owe  much  to  Graham  Lusk,  give  the 
higher  and  more  constant  value  of  3.6:1.  In  human 
diabetes,  the  quotient  is  less  than  that  of  Lusk  in  the 
greater  number  of  cases.  All  this  and  the  extra- 
ordinary constancy  of  the  values  in  animal  experi- 
ments give  to  this  finding  a  marked  biological  signifi- 
cance. It  is  another  question  whether  these  figures 
have  been  rightly  interpreted  and  whether  they  yield 
any  indication  as  to  the  manner  in  which  the  body 
utilizes  albumin  for  the  formation  of  sugar.  It  would 
have  to  be  assumed  that  after  removal  of  the  pancreas 
or  administration  of  maximal  doses  of  phloridzin  the 
body  ceases  to  oxidize  sugar,  or  that  the  tissues  have 
lost  the  capacity  to  utilize  sugar  at  all,  and  that  all  the 
sugar  which  is  produced  reappears  in  the  urine.  This 
is  in  harmony  with  the  views  as  to  the  type  of  dis- 
turbance in  diabetes  which  I  set  forth  in  my  New 


24        DISORDERS   OF   METABOLISM    AND   NUTRITION 

York  lectures  some  seven  years  ago.  It  has  been  ap- 
plicable to  diabetes  in  man  also.  There  is  however  a 
great  difficulty  in  bringing  phloridzin  diabetes  into  line 
with  the  other  conditions  and  the  more  we  learn  of 
phloridzin  diabetes  the  more  difficult  it  is.  To-day 
there  seems  but  little  doubt  that  phloridzin  glycosuria 
is  due  to  the  toxic  effects  of  the  phloridzin  on  the  renal 
epithelium  and  therefore  is  quite  of  a  different  origin 
from  the  pure  diabetic  glycosuria.  There  is  not  the 
slightest  evidence  for  the  assumption,  that  in  phlorid- 
zin poisoning  there  is  a  defect  in  the  oxidation  of 
sugar.  The  objection  may  be  advanced,  that  in 
phloridzin  intoxication  the  sugar  is  so  rapidly  and  com- 
pletely removed  from  the  blood  by  the  kidney  that 
none  remains  for  the  use  of  the  tissues  and  that  the 
cells  are  driven  to  draw  upon  the  fatty  substances  for 
their  demands  for  nitrogen-free  material.  This  criti- 
cism would  be  difficult  to  sustain,  however,  for  inves- 
tigations have  been  carried  out  in  my  clinic  which  show 
definitely  that  the  tissues,  and  the  muscles  especially, 
in  phloridzin  diabetes  do  not  utilize  and  oxidize  any 
material  other  than  carbohydrates.  Some  earlier  ob- 
servations made  in  my  clinic  proved  the  same  to  be  the 
case  in  pancreatic  diabetes.  I  merely  mention  these 
interesting  and  important  experiments  just  now ;  I  will 
return  to  them  later  on. 

If  the  tissues,  in  spite  of  the  diabetic  process,  con- 
tinue to  oxidize  carbohydrates,  then  the  quotient  D-i-N 
does  not  give  any  reliable  indication  as  to  the  condi- 
tions under  which  sugar  is  formed  from  albumin.     It 


NEW  ASPECTS  OF  DIABETES  25 

rather  shows  how  much  sugar  remains  in  proportion  to 
the  decomposed  albumin  after  the  organism  has 
covered  its  total  sugar  requirements  from  the  various 
sources  (albumin  and  fat).  It  is  remarkable  that  this 
quotient  exhibits  a  certain  constancy  in  maximal  pan- 
creas diabetes,  maximal  phloridzin  diabetes  and  in 
human  diabetes  on  typical  diets,  which  is  characteristic 
for  each  of  the  conditions.  We  are  quite  in  the  dark 
as  to  the  principle  which  underlies  this  constancy  but 
there  is  one  statement  we  can  make  with  safety  and 
that  is,  that  the  proportion  of  the  formation  of  sugar 
from  albumin  is  not  the  dominant  feature. 

C.  The  Fats 

There  are  no  various  views  as  to  the  formation  of 
sugar  from  glycerine,  which  is  a  component  of  fatty 
substances.  But  the  part  played  by  fatty  acids  has 
evoked  considerable  discussion.  Two  main  issues  are 
here  involved.  The  whole  question  is  so  important, 
not  only  from  the  standpoint  of  diabetes,  but  equally 
from  that  of  biological  chemistry  in  general,  that  we 
must  review  it  at  length. 

a.  The  Circulation  of  Fat 

We  are  now  in  position  to  state  more  confidently 
than  heretofore,  that  the  nitrogen- free  material  neces- 
sary for  muscle  metabolism  must  be  supplied  in  the 
form  of  sugar,  or  sugar- free  derivatives  (lactic  acid?), 
and  that  the  liver  is  the  place  where  the  muscle  foods 


26         DISORDERS   OF    METABOLISM    AND   NUTRITION 

are  prepared.  The  decomposition  of  albumin  and  the 
separation  of  its  carbohydrate  molecule  is  a  matter 
which  can  be  carried  out  most  probably  by  any  of  the 
cells  of  the  body.  The  cleavage  of  fat,  however  — 
if  we  exclude  bacterial  action  —  is  an  exclusive  func- 
tion of  the  liver.  At  least  we  are  not  aware  of  any 
evidence  which  points  to  the  collaboration  of  other 
organs. 

The  liver  receives  the  fat  —  which  it  has  to  work 
up  —  in  part  directly  from  the  food,  and  in  part  —  in- 
deed preferably  —  from  the  large  fat  deposits  of  the 
body  in  which  the  fat  is  deposited  with  astonishing 
rapidity  as  soon  as  it  passes  from  the  thoracic  duct 
into  the  blood  stream.  We  do  not  know  whether  the 
fat  which  results  from  an  excess  of  carbohydrate  food 
is  manufactured  in  the  fat  depots  themselves.  It 
seems  probable  that  the  liver,  when  its  glycogen  con- 
tent is  too  abundant,  builds  up  fat  and  that  this  fat 
is  carried  to  the  fat  stores.  On  the  other  hand,  the 
poverty  of  the  liver  cells  in  glycogen  may  indicate  the 
time  and  season  for  the  commencement  of  the  manu- 
facture of  sugar  out  of  fat.  Then  will  follow  a  vig- 
orous re-transport  of  fat  from  the  fat  stores  to  the 
liver  cells.  During  inanition  the  blood  becomes  richer 
in  fats,  because  the  individual  is  living  on  his  own 
body  fat  and  it  is  necessary  to  transfer  this  to  the 
liver  for  the  process  of  manufacture.  If  in  a  starving 
animal  great  demands  are  made  upon  the  liver  for  the 
formation  of  sugar,  as,  for  instance,  in  phloridzin 
diabetes,  then  the  fat  transport  is  increased.     Then 


NEW  ASPECTS  OF  DIABETES  27 

follows  a  fatty  infiltration  of  the  liver  from  the  pres- 
sure of  streams  of  incoming  material  from  all  quar- 
ters. When  the  phloridzin  administration  is  stopped 
and  large  amounts  of  carbohydrates  are  given,  then  the 
fat  returns  again  rapidly  to  the  fat  depots.  As  Rosen- 
feld  has  shown,  glycogen  is  the  antithesis  of  fat  and  fat 
the  enemy  of  glycogen.  In  severe  cases  of  diabetes 
there  is  visible  evidence  of  the  transport  of  fat  in  the 
blood  to  the  liver  in  the  lipaemia  which  often  occurs; 
this  means,  that  all  the  possible  reserves  are  drawn 
upon  in  order  to  avert  the  extreme  and  dangerous 
stages  of  the  diabetic  process.  These  and  many  other 
facts  in  physiology  and  pathology  appear  clear  and 
intelligible  in  the  light  of  the  theory  advanced.  I 
believe  that  the  conditions  may  be  more  easily  compre- 
hended if  we  consider  the  problem  from  the  stand- 
point of  metabolism  in  starvation.  Here  the  tissues 
are  limited  to  the  using  up  of  their  own  substance  for 
the  production  of  the  necessary  calories.  At  the  com* 
mencement  of  the  hunger  period  there  is  a  small 
quantity  of  glycogen  available,  partly  in  the  liver  and 
partly  in  the  muscles.  This  store  is  soon  exhausted 
and  after  about  two  days  of  hunger  the  body  is  prac- 
tically devoid  of  glycogen.  In  such  a  case,  protein 
and  fat  are  the  only  material  available  for  oxidation. 
An  adult  healthy  man  utilizes  about  70  grams  albumin 
per  day;  this  yields  about  350  calories;  the  70  grams 
of  albumin  will  yield  at  the  utmost  55  grams  of  sugar. 
The  starving  adult  man  requires  many  more  calories, 
at  least  2000-2500  according  to  his  size  and  work. 


28        DISORDERS   OF   METABOLISM    AND   NUTRITION 

After  the  protein  has  been  made  to  yield  its  calories, 
there  still  remains  about  1650-2250  calories  to  pro- 
vide for.  These  have  to  be  obtained  through  the 
oxidation  of  fat;  180-240  grams  of  fat  will  supply 
the  necessary  calories.  In  support  of  the  statement 
that  fat  is  the  substance  used  at  this  time  and  that  no 
other  material  except  a  small  amount  of  proteid  is 
pressed  into  service,  and  that  these  bodies  are  carried 
to  the  end  stages  of  oxidation,  we  find  that  the  so- 
called  "  respiratory  quotient "  falls  to  730-750, 
whereas  with  the  exclusive  oxidation  of  carbohydrates 
the  value  is  1000  and  with  a  mixture  of  albumin,  fat 
and  carbohydrate,  the  figures  vary  from  800-850. 

h.  Does  Muscle  Tissue  Oxidize  Fat? 

Up  to  this  point  there  is  complete  unanimity  on  the 
part  of  all  physiologists  and  pathologists.  But  from 
here  opinions  dijffer. 

Some  hold  the  opinion  that  when  circumstances  arise 
in  which  carbohydrates  no  longer  are  at  the  disposal 
of  the  body,  the  cells,  and  especially  the  muscle  cells, 
alter  their  usual  way  of  living  and  oxidize  the  fat 
brought  to  them  by  the  blood  stream  at  once,  as  in 
ordinary  conditions  of  nutrition  they  oxidize  predomi- 
nantly or  exclusively  carbohydrates.  This  view  is  very 
difficult  to  maintain  because  the  relatively  simple  chem- 
istry of  muscle  tissue  does  not  furnish  a  tittle  of  evi- 
dence as  to  type  of  decomposition  which  is  under- 
gone by  fat,  in  the  muscle  cells.  That  there  is  a  com- 
plete oxidation  to  CO2  and  H2O  is  out  of  question, 


NEW  ASPECTS  OF  DIABETES  29 

but  we  could  expect  to  find  intermediary  bodies  formed 
during  the  fat  cleavage.  About  this  there  is  prac- 
tically nothing  known.  We  only  know  that  there  is 
an  oxidation  of  carbohydrates  and  there  is  some  evi- 
dence that  muscle  tissue  plays  a  part  in  the  attacks 
upon  the  foundation  stones  of  the  albumin  molecule. 
O.  Nasse  advanced  those  views  some  forty  years  ago 
and  they  still  form  the  basis  of  muscle  chemistry  to 
this  very  day.  All  attempts  made  by  chemists  to  get 
a  grasp  of  the  action  of  the  muscle  cell  upon  fat 
molecules  have  failed  signally.  Nevertheless  the  teach- 
ing that  during  a  period  of  carbohydrate  deficiency  the 
muscles  oxidize  fatty  materials,  has  been  clung  to  most 
stubbornly  and  it  has  exerted  a  powerful,  and  to  me  a 
highly  unfavorable  influence  upon  the  progress  of  our 
knowledge  of  diabetic  processes. 

The  second  hypothesis  is  that  sugar  serves  the 
muscle  cell  as  food  only,  and  what  is  more,  also  then 
if  the  food  contains  hardly  any  carbohydrate  and  the 
glycogen  stores  are  used  up.  In  this  category  must 
be  placed  every  individual  who  consumes  protein  and 
fat  alone  and  this  is  the  ordinary  diet  of  many  tribes 
of  the  far  North  and  of  all  beasts  of  prey.  The  in- 
dividual undergoing  starvation  comes  under  the  same 
heading;  while  diabetics  on  restricted  dietaries  and 
those  suffering  from  severe  diabetes  who  excrete  more 
sugar  than  the  amount  represented  by  the  intake  of 
carbohydrates  must  be  similarly  classed. 

O.  Nasse  in  his  time  put  forward  the  view,  that 
when  carbohydrates  were  absent  the  muscle  cell  con- 


30         DISORDERS   OF   METABOLISM    AND   NUTRITION 

tinned  to  bum  sugar  and  sugar  only,  but  he  did  not 
develop  the  hypothesis  very  fully,  and  it  did  not  there- 
fore make  any  lasting  impression  upon  physiologists. 
I.  Seegen  pushed  the  question  more  vigorously,  and 
to-day  we  recognize  that  his  findings  very  closely  ap- 
proached what  we  now  consider  as  the  right  stand- 
point. Unfortunately,  Seegen  supported  his  conten- 
tions with  so  imperfect  and  unreliable  methods,  that  his 
experiments  would  not  stand  criticism,  and  the  critics 
who  rightly  condemned  his  experiments,  cast  also  his 
conclusions  and  his  theories  to  the  winds. 

Already  twenty  years  ago  I  supported  Seegen's 
hypothesis,  that  when  starving  men,  or  men  living  on 
protein  and  fat  only,  undertake  muscular  work  and 
burn  up  a  certain  quantity  of  fat  the  decomposition 
of  the  fat  does  not  occur  in  the  muscle  cell  itself,  and 
I  went  further,  and  said,  that  it  was  necessary  for  the 
fat  to  be  worked  up  into  sugar  elsewhere  before  it 
could  serve  as  food  for  the  muscle  cells.  The  liver 
was  suggested  as  the  place  where  the  change  took  place ; 
it  was  elsewhere  thought,  that  the  change  was  a  faculta- 
tive one,  that  is  to  say,  that  this  was  not  the  case  at 
all  times  and  seasons,  but  only  when  the  liver  did  not 
command  sufficient  glycogen  to  provide  the  require- 
ments of  the  blood  and  tissues  for  sugar. 

The  formation  of  sugar  from  fat  is  closely  associ- 
ated with  two  factors: 

c.  Limits  of  Sugar  Formation  from  Fat 
Glycogen  is  not  formed  during  the  process.     One  has 


NEW   ASPECTS   OF  DIABETES  3 1 

fed  animals  with  the  various  forms  of  fat  and  trans- 
fused various  fatty  acids  and  their  salts  through  the 
portal  veins  of  isolated  and  surviving  livers,  and  also 
mixed  fresh  emulsions  of  liver  cells  with  fatty  acids; 
in  not  a  single  instance  has  the  smallest  quantity  of 
glycogen  been  demonstrable.  These  findings  have  been 
used  as  an  argument  against  the  formation  of  sugar 
from  fat;  such  a  contention  goes,  however,  too  far. 
The  experiments  show  only,  that  after  flooding  the 
liver  with  fatty  acids,  glycogen  is  not  deposited  in  the 
cells.  That  leaves  the  question  of  sugar  formation  an 
open  one.  To  my  mind,  the  results  of  the  experiments 
may  be  stated  differently:  The  normal  healthy  liver 
only  forms  carbohydrates  out  of  fat  when  it  is  neces- 
sary to  do  so  to  maintain  the  normal  content  of  the 
blood  and  supply  the  needs  of  the  tissues.  This  comes 
practically  to  what  I  have  said  before,  namely,  that  the 
formation  of  sugar  from  fat  is  a  facultative  process. 
It  puts  it  into  the  position  of  an  act  of  necessity  when 
other  material  is  unavailable;  it  does  not  overstep  the 
bounds  of  necessity.  Whether  the  formation  of  sugar 
from  fat  is  a  direct  one  without  passing  through  the 
glycogen  stage  or  whether  glycogen  is  formed  and  rap- 
idly broken  up  and  passed  into  the  blood  as  dextrose 
must  be  left  an  open  question.  I  consider  the  first  to 
be  the  more  likely  process.  The  fact  that  in  the  healthy 
individual  a  large  quantity  of  sugar  exceeding  the 
amount  required  does  not  originate  from  fat  is  of  gen- 
eral biological  interest.  The  liver  does  not  receive  the 
fat  which  it  utilizes  directly  from  the  fat  contained  in 


32         DISORDERS   OF   METABOLISM    AND   NUTRITION 

food,  or  at  all  events,  only  to  a  slight  extent.  The  fat 
of  the  food  streams  through  the  thoracic  duct  into  the 
blood  and  disappears  rapidly  from  the  blood  into  the 
large  fat  depots.  The  liver  receives  only  a  very  small 
fraction. 

If  the  liver  manufactures  sugar  in  unlimited  quanti- 
ties from  the  fat  present  in  the  food,  or  from  the  fat 
streaming  in  from  the  fat  stores,  then  it  becomes  neces- 
sary for  the  organism  immediately  to  transform  the 
carbohydrate  again  into  fat.  For  the  use  of  sugar  by 
the  tissues  is  a  limited  one;  it  is  one  of  the  best  recog- 
nized principles  of  physiology  that  any  excess  of  carbo- 
hydrates is  quickly  converted  into  fat.  We  overfeed 
animals  and  men  with  carbohydrates  and  v^e  gain  fat. 
All  these  chemical  changes  call  for  work  and  energy 
exchange.  It  would  be  a  squandering  of  potential 
energy  if  fat  were  first  changed  into  stored  glycogen 
and  then  reconverted  into  fat,  while  it  is  an  economy 
that  the  manufacture  of  sugar  from  fat  is  carried  on 
only  to  provide  for  the  immediate  needs. 

d.  Decomposition  of  Fat  and  Acetone  Bodies 

A  second  characteristic  of  the  hepatic  formation  of 
sugar  from  fat  is  the  appearance  of  acetone  bodies  as 
by-products.  This  process  is  not  restricted  to  the 
decomposition  of  fat  alone,  for  it  plays  a  part  also  in 
the  cleavage  of  the  aminoacids  from  the  albumin  mole- 
cule. This  was  first  demonstrated  by  G.  Embden  and 
his  colleagues  in  my  Frankfurt  laboratory.     It  is  prob- 


NEW  ASPECTS  OF  DIABETES  33 

able  that  certain  parts  of  the  fatty  acid  molecule  may 
be  amidised  before  they  are  broken  down  further.  If 
this  supposition  be  confirmed,  then  we  shall  be  able  to 
state  the  formation  of  acetone  bodies  from  albuminates 
and  fatty  acids  in  uniform  chemical  formulae.  There 
seems  little  doubt  to-day  but  that  acetone  bodies  occur 
during  normal  intermediate  metabolism,  but  most 
probably  in  limited  bounds  only.  Under  ordinary  con- 
ditions they  are  at  once  further  decomposed.  If  we 
review  the  entire  circumstances  under  which  acetone 
and  B-oxybutyric  acid  appear,  we  meet  always 
one  important  fact :  under  all  these  conditions  is  glyco- 
gen absent,  or  nearly  absent,  from  liver  cells ;  we  shall 
not  be  going  too  far  if  we  venture  the  sentence  —  the 
presence  of  glycogen  in  liver  cells  hinders  the  forma- 
tion of  acetone  bodies  or  hastens  their  further  decom- 
position. Embden's  experiments  go  far  to  verify  this 
statement. 


e.  Arguments  for  and  against  the  Formation  of  Sugar 
from  Fat 

In  the  above  we  accepted  the  formation  of  sugar 
from  fat  as  an  established  principle.  This  is  by  no 
means,  however,  generally  recognized.  When,  twenty 
years  ago,  I  found  new  grounds  for  supporting  the 
older  teaching  of  Seegen  I  was  quite  alone  in  my  con- 
tentions and  together  with  my  pupils  had  to  defend  this 
principle,  so  equally  important  for  both  physiology  and 
pathology.     First  some  time  later,  E.  Pfliiger  lent  the 


34         DISORDERS   OF    METABOLISM    AND   NUTRITION 

theory  his  strong  support ;  in  spite  of  this,  the  view  has 
not  to-day  gained  wide  recognition ;  in  fact,  with  a  few 
exceptions — Th.  Rumpf,Lenne  —  all  the  modern  work- 
ers upon  diabetes  dissent  from  it.  I  have  to  complain, 
that  although  many  facts  have  been  brought  forward 
in  support  of  the  above-mentioned  theory,  yet  always 
the  same  old  reasons  have  been  opposed  to  it.  I  must 
deal  with  the  several  objections  and  arguments  in 
further  detail. 

(i)  It  is  argued  that  chemistry  has  not  been  able 
to  show  a  way  by  which  a  fatty  molecule  may  yield 
sugar.  This  is  quite  right,  but  the  opposite  is  also  true. 
We  do  not  know  the  chemical  means  by  which  sugar 
is  converted  into  fatty  acids  and  yet  the  formation  of 
fat  from  carbohydrates  is  one  of  the  fundamental  facts 
of  biology.  This  so  impressed  itself  upon  the  minds 
of  observers  and  investigators,  that  already  in  the  early 
days  of  biology  it  became  a  fundamental  axiom.  Still 
to-day  we  know  little  more  of  the  details  of  the  chem- 
ical processes  than  did  the  first  workers.  If  then  in 
the  organism  sugar  is  transformed  into  fat  by  an  un- 
known chemical  method,  may  we  not  with  safety  ac- 
cept that  a  transformation  in  the  opposite  direction  is 
equally  possible?  All  the  fermentative  processes  oc- 
curring in  animals  and  plants  which  serve  to  bring 
about  molecular  changes,  are  reversible  in  nature.  We 
see  this  in  the  building-up  and  breaking-down  of  albu- 
mins, purin  bodies  and  carbohydrates,  while  in  plant 
life  there  is  the  convincing  and  satisfactory  process  of 
the  interchange  between  fat  and  carbohydrate.     At  all 


NEW  ASPECTS  OF  DIABETES  35 

events,  in  denying  the  occurrence  of  the  transforma- 
tion it  is  an  entirely  unscientific  attitude  to  do  this 
solely  because  we  are  ignorant  of  the  exact  chemical 
details  of  the  process. 

(2)  It  has  been  urged  that  fat  does  not  yield  glyco- 
gen. This  statement  is  also  correct.  As  we  have  al- 
ready observed,  it  does  not  follow  therefore  that  fat 
does  not  yield  sugar.  I  have  shown  that  from  the 
standpoint  of  the  energy  exchange  it  is  an  intelligible 
act  of  economy,  if  fat  is  used  only  for  the  immediate 
needs  and  not  for  the  purpose  of  building  up  a  reserve- 
stock  of  carbohydrates. 

(3)  One  has  referred  to  the  quotient  D-f-N  and  in- 
sisted, that  in  the  urine  of  a  patient  upon  a  carbo- 
hydrate-free diet  there  occurs  no  more  sugar  than 
would  be  expected  from  the  decomposition  of  albumin 
according  to  chemical  calculations.  (Index:  the 
amount  of  nitrogen  in  the  urine,)  No  further  source 
for  the  sugar  be  therefore  required. 

This  view,  that  the  urinary  sugar  corresponds  to  the 
maximal  quantity,  which  according  to  theory,  may  be 
derived  from  albumin,  is  unconditionally  right  for 
phloridzin  diabetes,  for  experimental  pancreas  dia- 
betes, and  for  all  slight,  as  well  as  for  some  of  the  se- 
vere forms  of  human  diabetes.  It  is  not  correct, 
however,  for  a  certain  number  of  severe  cases.  As  we 
have  shown,  the  maximal  amount  of  sugar  obtainable 
from  albumin  corresponds  to  one  part  of  nitrogen  to 
five  parts  of  glucose.  Now  there  are  records  of  a 
number  of  cases,  and  mostly  from  my  clinic,  in  which 


36        DISORDERS   OF   METABOLISM   AND   NUTRITION 

the  quotient  D^N  not  only  temporarily  but  for  a 
long  time  reached  a  higher  level  than  5:1,  in 
spite  of  starch-free  food.  As  under  these  conditions 
there  is  no  other  source  for  the  sugar,  the  extra  sugar 
must  be  ascribed  to  a  fatty  origin.  Against  the  pre- 
cision and  reliability  of  these  clinical  experiments  many 
objections  have  been  made,  but  the  overscrupulous 
critic  is  bound  to  admit  that  consequently  the  later  ob- 
servations have  been  carried  out  with  even  much 
greater  exactness  and  care  than  the  earlier  ones.  Even 
if  we  accept  the  criticism  upon  some  of  the  observa- 
tions, there  still  remain  a  sufficient  number  of  cases  in 
which  it  is. safe  to  assume  the  necessity  for  a  source  of 
sugar  other  than  that  of  the  carbohydrates  and  al- 
bumin. 

As  I  have  already  mentioned,  all  the  conclusions 
drawn  from  a  consideration  of  the  quotient  D^-N  pos- 
tulate, that  the  sugars  which  are  formed  in  diabetics  — 
animal  or  human  —  are  excreted  in  the  urine,  and  that 
the  tissues  have  lost  the  property  of  sugar  oxidation. 
One  regards  this  assumption  as  a  correct  one,  because 
in  severe  diabetes  the  respiratory  quotient  falls  very 
low  and  approaches  the  value  which  would  express  the 
total  oxidation  as  from  fat.  In  reality,  however,  this 
proves  only  that  fat  was  the  primary  material  attacked 
by  the  oxidation  process;  it  does  not  in  the  slightest 
degree  indicate  what  is  the  type  of  cleavage  of  the 
atomic  groups  of  the  fatty  molecule  in  the  intermediary 
metabolism.  The  respiratory  quotient  does  not  teach 
us  whether  certain  parts  of  the  fat  molecule  were 


NEW   ASPECTS   OF   DIABETES  37^ 

transformed  into  sugar  before  the  oxidation  to  car- 
bonic acid  and  water  was  finished. 

Here  I  may  mention  some  recent  experiments  which 
have  been  carried  out  in  my  laboratory  by  H.  Salomon 
and  O.  Porges.  As  a  basis  we  accepted  the  statement 
that  the  change  of  fat  into  sugar  occurs  in  the  liver 
alone.  If  this  is  correct,  thn  the  exclusion  of  the 
liver  from  the  circulation  would  remove  the  influence 
which  the  fat  exchange  in  the  liver  exerts  upon  the 
respiratory  quotient.  We  hoped  then  to  discover  what 
materials  were  oxidized  in  the  other  tissues.  Should 
the  tissues,  and  especially  the  muscles,  be  able  to  com- 
bine directly  with  the  fatty  acid  molecule  and  to  ox- 
idize it  after  the  abdominal  organs  had  been  excluded 
from  the  domination  of  the  respiratory  exchanges,  then 
the  respiratory  quotient  would  remain  at  a  low  level. 
As  a  matter  of  fact,  immediately  the  liver  is  cut  off 
from  the  circulation,  the  quotient  reaches  i,  which  is 
practically  the  figure  yielded  by  the  oxidation  of  sugar. 
This  was  first  obtained  with  a  healthy  animal,  and  later 
with  animals  the  subjects  of  pancreas  diabetes  and 
maximal  phloridzin  diabetes.  On  the  other  hand,  con- 
trol experiments  were  made  with  an  Eck's  fistula.  In 
this  instance  also,  the  respiratory  quotient  rose,  al- 
though not  to  the  same  height  as  in  the  previously 
cited  experiments.  This  is  what  would  be  expected, 
as  an  Eck's  fistula  does  not  exclude  the  liver  from  the 
circulation  entirely,  but  only  in  part.  The  experiments 
gave  results  which  were  the  same  in  healthy  animals 
or  in  animals  with  severe  diabetes.     We  find  therefore 


38         DISORDERS   OF   METABOLISM    AND   NUTRITION 

that  after  the  exclusion  of  the  liver  the  muscle  cells 
oxidize  carbohydrates  only  and  that  this  characteristic 
is  not  altered  even  in  severe  diabetes.  These  experi- 
mental results  are  important  both  for  physiology  and 
science  of  diabetes.  It  is  apparent,  therefore,  that  all 
conclusions  based  upon  the  effect  of  the  quantitative 
relations  of  albumin  and  sugar  formation  on  the  quo- 
tient D-i-N  must  fall  to  the  ground. 

D.  Summary 

These  arguments  and  facts  so  far  brought  forward 
tend  to  show,  that  in  addition  to  carbohydrates,  pro- 
teins and  fats  contribute  to  the  formation  of  sugar. 
The  share  of  the  protein  and  fat  is  not,  however,  an 
equal  one.  Quantitatively,  the  part  played  by  the  al- 
bumin itself  in  the  formation  of  sugar  is  not  great. 
About  100  grams  is  an  average  daily  albumin  exchange 
in  man ;  at  the  most  this  would  only  yield  60-70  grams 
of  sugar  and  probably  the  amount  is  very  much  less. 
This  is  a  small  quantity  for  the  metabolic  needs  of  a 
resting  adult,  let  alone  that  of  a  man  in  full  work.  In 
addition,  proteins  exert  an  irritant  action  upon  the 
sugar- forming  organs;  some  proteins  act  more  in- 
tensely than  others ;  they  may  be  looked  upon  as  a  whip 
to  the  diastatic  processes.  In  the  healthy,  the  well- 
regulated  mechanism  of  the  sugar  production  is  not 
affected  by  this  irritation,  but  when  the  mechanism  is 
not  well  regulated  there  is  a  definite  response  to  the 
smart.     This  has  been  quoted  at  full  length.     Fats,  on 


NEW  ASPECTS  OF  DIABETES  39 

the  other  hand,  do  not  irritate  the  sugar-producing  cen- 
ters ;  they  do  not  incite  the  liver  to  manufacture  sugar. 
The  liver  uses  fats  for  the  purpose  of  forming  sugar 
only  when  the  poverty  of  other  materials  makes  it 
necessary. 


11.  THE  RISE  IN  CALORIC  PRODUCTION  AND 
ITS  CAUSES 

It  is  generally  accepted  that  in  severe  diabetes  the 
processes  of  oxidation,  or,  in  other  words,  the  pro- 
duction of  calories  is  increased.  Why  is  this  the  case  ? 
To-day  we  are  accustomed  to  regard  endogenous  fac- 
tors as  the  cause  of  this  increase  in : 

1.  Basedow's  disease,  feeding  with  thyroid  gland, 
and  spontaneous  and  artificial  hyperthyroidism. 

2.  In  severe  diabetes  in  man. 

3.  In  experimental  diabetes  and  pancreatic  ablation. 

4.  In  high  pyrexia  (man  and  animals). 

5.  In  some  cases  of  acromegaly. 

Do  the  causes  of  the  increased  oxidation  differ  in 
these  five  cases  or  is  there  a  bridge  by  means  of  which 
we  may  connect  them  together?  I  am  of  the  opinion 
that  the  latter  is  probable.  The  advances  made  in  our 
knowledge  of  the  internal  secretions  have  shown  that 
certain  inter-relations  come  into  play.  The  investiga- 
tions made  by  my  assistants,  Eppinger  and  Falta,  re- 
vealed, among  other  things,  the  inter-actions  of  the 
pancreas  and  the  thyroid  gland.  Both  exhibit  a  type 
of  opposition  to  one  another,  for  instance,  in  hyper- 
thyroidism the  function  of  the  pancreas  is  depressed 
and  alimentary  glycosuria  is  easily  brought  about.  On 
the  other  hand,  in  atrophy  or  hypoplasia  of  the  thyroid 
gland  the  pancreatic  powers  are  increased  and  patients 

40 


NEW   ASPECTS   OF  DIABETES  4 1 

suffering  from  these  diseases  —  for  instance,  myx- 
cedema  —  can  take  large  quantities  of  glucose  without 
the  slightest  glycosuria.  The  influence  of  the  thyroid 
gland  is  seen  also  in  the  alterations  of  the  external  se- 
cretions of  the  pancreas,  although  this  is  less  common. 
In  Basedow's  disease,  there  is  often  a  "  fatty  diar- 
rhoea "  due  to  the  insufficiency  of  pancreatic  ferments. 
In  all  these  cases  there  is  either  a  spontaneous  glyco- 
suria, or  at  least  a  spontaneous  hyperglycsemia  and  a 
tendency  to  glycosuria.  When  the  Basedow's  con- 
dition improves,  the  fatty  diarrhcea  and  glycosuria  dis- 
appear ;  in  two  cases  we  were  able  to  diminish  the  size 
of  the  thyroid  by  Rontgen  rays ;  the  evidences  of  Base- 
dow's disease  became  less  prominent  and  the  alimen- 
tary glycosuria  was  no  more  demonstrable. 

The  relations  between  the  glands  possessing  internal 
secretions  are  many-sided.  The  thyroid  can  be  influ- 
enced by  the  pancreas,  and  so  we  are  not  surprised  to 
find  that  the  moment  the  pancreas  is  ablated  the  thy- 
roid functions  gain  the  upper  hand ;  there  is  increased 
oxidation,  that  typical  symptom  of  hyperthyroidism. 
Thus  the  thyroid  acts  upon  oxidation  as  a  pair  of  bel- 
lows rejuvenates  a  fire.  That  the  principles  which  de- 
termine the  important  effects  following  extirpation  of 
the  pancreas  may  be  applied  to  the  condition  of  severe 
diabetes  in  man  goes  without  saying.  We  may  assign 
the  increases  in  the  caloric  production  in  the  disease  to 
the  loss  or  diminution  of  the  inhibitory  factors,  radi- 
ating into  the  thyroid  through  the  chemical  correlation 
of  the  pancreas. 


42         DISORDERS   OF   METABOLISM    AND   NUTRITION 

We  may  perhaps  also  attribute  the  increased  oxida- 
tion which  we  often  —  though  not  always  —  meet  with 
in  pyrexia  to  a  chemical  irritation  of  the  thyroid  gland, 
in  other  words,  to  a  toxogenous  (or  pyogenous)  hy- 
perthyroidism. In  febrile  infectious  diseases  there  are 
many  symptoms  which  also  occur  in  Basedow's  disease ; 
tendency  to  sweating,  abnormal  irregularity  of  the 
cardio-vascular  nerves,  increased  frequency  of  pulse, 
and  above  all,  that  cardinal  symptom  of  Basedow's  dis- 
ease, the  augmented  oxidation  processes.  In  spite  of 
a  precise  and  almost  primeval  acquaintance  with  the 
symptoms  of  fever,  the  pathogenesis  of  the  condition 
is  not  yet  sufficiently  clear,  and  we  can  to-day  only  put 
into  the  form  of  hypothesis  the  thought,  that  the  symp- 
tom-complex of  fever,  and  especially  the  raised  caloric 
production,  is  intimately  associated  with  a  toxic  irrita- 
tion of  the  thyroid  tissues.  This  hypothesis  gains  sup- 
port from  the  fact  that  in  fever  there  occurs  regularly 
a  demonstrable  hyperglycsemia  and  very  frequently  a 
tendency  to  alimentary  glycosuria.  During  an  attack 
of  pneumonia  or  of  erysipelas  patients  sometimes  ex- 
crete 8  to  12  grams  of  sugar  after  an  intake  of  lOO 
grams  of  glucose,  while  at  the  end  of  the  attack  large 
quantities  of  carbohydrates  and  sugar  can  be  con- 
sumed without  a  slightest  trace  of  glycosuria.  This 
surely  indicates  a  febrile  insufficiency  of  the  pancreas 
and  we  have  to  consider:  i,  whether  the  infectious 
intoxication  irritates  the  thyroid  first;  or  2,  whether 
the  pancreas  is  the  first  to  be  damaged,  and  as  a  result 
of  this  defect  there  is  a  marked  excitation  of  the  thy- 


NEW  ASPECTS  OF  DIABETES  43 

roid;  or  3,  whether  both  organs  are  affected  at  the 
same  time,  although  independently,  the  thyroid  in  the 
sense  of  an  irritation,  the  pancreas  in  such  of  a 
paralysis. 

That  the  pancreas  will  be  damaged  in  various  ways 
by  the  several  infections  is  quite  natural;  the  hurt  most 
probably  takes  the  form  of  a  degeneration  such  as  is 
generally  met  with  in  glandular  organs  in  infectious 
diseases. 

For  many  years  I  have  held,  that  the  marked  ali- 
mentary hyperglycaemia  and  glycosuria  in  fever  must 
be  regarded  from  this  standpoint,  and  now  we  come 
more  and  more  in  our  findings  in  diabetes  to  see  that 
the  connection  between  diabetes  and  the  acute  in- 
fectious conditions,  such  as  angina,  influenza,  measles 
and  scarlet  fever  is  so  direct  and  evident  that  we  can- 
not deny  the  possibility  of  some  intermediate  setiolog- 
ical  factor. 

We  commenced  these  remarks  with  the  discussion 
upon  the  formation  of  sugar  from  albumin.  We  have 
seemed  to  get  wide  off  our  theme,  but  it  is  only  an  ap- 
parent extension.  In  reality,  this  apparently  simple 
question  is  very  complicated.  We  soon  get  into  a 
blind  alley,  if  we  regard  our  theme  from  a  purely  chem- 
ical aspect  alone  and  only  considered  the  chemical  con- 
ditions which  determine  the  pathway  of  aminoacids  to 
carbohydrates.  We  do  not  know  to-day  what  the  de- 
tails of  these  processes  are ;  on  the  other  hand,  I  have 
shown,  that  the  increased  formation  of  sugar  which 
follows  the  ingestion  of  proteins  and  aminoacids  is 


44        DISORDERS   OF   METABOLISM   AND   NUTRITION 

bound  up  with  important  questions  of  metabolism,  and 
that  the  anomalies  observed  in  diabetic  metabolism  are 
only  placed  in  their  right  light  when  analogous  meta- 
bolic changes  in  other  diseases  are  investigated  at  the 
same  time. 


III.  THE  CONTROL  OF  SUGAR  FORMATION 
AND  ITS  DISTURBANCES  —THE- 
ORY OF  DIABETES 

A.  The  Liver  as  the  Place  of  Control 

The  control  of  sugar  formation  and  its  distribution 
takes  place  in  the  liver.  The  other  organs  elaborate 
and  consume  sugar,  but  do  not  share  in  its  production. 
The  cells  of  the  glands,  and  still  more  those  of  the 
muscles,  have  a  certain  local  controlling  power,  in  so 
far  as  they  are  able,  when  there  is  over-production,  to 
take  up  a  small  reserve  of  glycogen.  It  is  left  to  the 
liver,  however,  to  supply  the  organism  in  general  with 
sugar.     The  following  processes  occur  in  the  liver: 

1.  The  taking  up  of  carbohydrates  streaming  in 
from  the  intestinal  canal  through  the  portal  vein. 

2.  Their  conversion  into  glycogen,  and  perhaps  into 
fat,  when  there  is  a  great  excess.  As  we  have  said, 
it  is  not  certain  whether  the  liver  can  form  fat  out  of 
carbohydrates,  or  whether  this  is  the  only  organ  in 
which  this  process  takes  place. 

3.  When  there  is  a  very  rapid  and  extensive  supply 
of  sugar  to  the  liver,  a  portion  escapes  conversion  into 
glycogen  and  this  leads  to  hyperglycsemia  and  eventu- 
ally to  alimentary  glycosuria. 

4.  Intra-hepatic  decomposition  of  protein  leads  to 
sugar  formation.  The  details  of  this  chemical  process 
are  unknown.     Perhaps  it  is  more  a  stimulus  to  sugar 

45 


46         DISORDERS   OF    METABOLISM    AND    NUTRITION 

formation  which  occurs,  and  not  a  direct  conversion 
of  the  protein  nuclei  into  sugar. 

5.  If  the  remaining  materials,  the  available  carbo- 
hydrates, and  in  the  last  resort,  the  protein  nuclei,  are 
insufficient  for  the  needs  of  the  moment,  sugar  is 
formed  from  fat. 

6.  A  diastatic  process  by  which  the  glycogen  in  the 
liver  is  re-converted  into  sugar.  Glucose  is  formed, 
and  leaves  the  liver  by  the  hepatic  vein. 

Which  particular  material  gives  rise  to  sugar  is  not 
important  from  our  present  point  of  view.  We  must 
regard  sugar  formation  in  the  liver  as  a  single  process, 
which  has  for  its  object  the  maintenance  of  the  sugar 
content  of  the  blood  at  a  constant  height,  and  likewise 
the  supplying  of  sugar  to  the  tissues.  The  amount  of 
sugar  metabolized  in  the  tissues  varies  enormously. 
During  complete  rest  it  is  at  its  minimum;  work  in- 
creases it  two  or  three  times  over,  or  more.  The 
sugar  content  of  the  blood  nevertheless  remains  at 
about  the  same  level,  namely  about  70  to  90  centigrams 
of  glucose  in  one  liter  of  blood.  It  falls  a  little  (to 
about  50  to  60  centigrams)  only  as  a  result  of  pro- 
longed and  laborious  muscular  work.  Then  the  sugar 
is  so  rapidly  used  up  that  the  production  cannot  keep 
pace  with  the  loss.  This  synchronizes  with  a  feeling  of 
actual  bodily  fatigue,  and  a  desire  for  rest.  All  in- 
vestigations of  working  men  and  animals,  and  of  the 
isolated  hearts  of  cold-  and  warm-blooded  animals, 
show  that  carbohydrates,  and  especially  sugar,  are  the 
best  materials  for  retarding  or  abolishing  muscular  fa- 


NEW  ASPECTS   OF  DIABETES  47 

tigue.  It  is  easy  to  understand  the  prophylactic  influ- 
ence of  sugar  food.  It  is  the  material  most  easily  ab- 
sorbed, and  most  easily  and  quickly  converted  into 
blood  sugar  by  the  liver,  whilst  the  formation  of  sugar 
from  protein  and  fat  must  certainly  take  up  more  en- 
ergy and  probably  also  more  time. 

The  normal  control  of  sugar  formation  results  in  a 
small  supply  during  rest  and  a  copious  supply  during 
work,  as  it  has  to  adapt  the  amount  yielded  to  the 
blood  to  the  amount  required  by  the  tissues.  We  do 
not  know  the  signal  by  which  the  liver  is  informed  as 
to  how  much  sugar  it  ought  to  set  free.  Possibly  the 
sugar  content  of  the  hepatic  artery  provides  the  signal ; 
possibly  the  metabolic  products  of  the  cells  of  the 
muscles  and  glands  perform  this  duty.  But  the  proc- 
ess is  very  likely  far  more  complicated.  The  signals, 
that  is  to  say,  are  not  transmitted  directly  to  the  liver, 
but  are  first  passed  through  the  pancreas  or  suprare- 
nals,  both  of  which  exert  a  controlling  influence  on  the 
sugar  production  of  the  liver.  Whatever  path  these 
signals  take,  however,  we  can  state  with  certainty  that 
normally  they  originate  in  the  tissues ;  in  other  words, 
it  is  the  requirements  of  the  tissues  which  form  the 
supreme  and  perhaps  the  only  factor  in  regulating  in 
amount  of  sugar  formation. 

For  these  processes  to  maintain  their  normal  course, 
we  must  assume  a  normal  degree  of  excitability  in  the 
sugar  factory  in  the  liver.  The  general  expression 
"sugar  factory,"  or  sugar  mechanism,  will  be  em- 
ployed henceforth,  because  it  commits  us  to  nothing, 


48        DISORDERS   OF   METABOLISM   AND   NUTRITION 

and  because  the  words  "  diastatic  process,"  commonly 
used,  do  not  cover  the  entire  extent  of  the  sugar-form- 
ing activities  of  the  liver. 

The  excitability  of  the  sugar  factory  is  not  uni- 
formly great,  and  only  depends  to  a  very  small  degree 
on  the  condition  of  the  liver  itself.  One  might  im- 
agine, that  so  delicately  adjusted  a  mechanism  as  the 
control  of  the  sugar  production  must  be  seriously  dam- 
aged when  the  organ  in  which  it  takes  place  is  dis- 
eased. This,  however,  is  not  the  case  —  on  the  con- 
trary—  carbohydrate  metabolism  usually  goes  on 
pretty  well  normally  in  most  diseases  of  the  liver. 
The  only  abnormality  which  we  can  detect  is  a  stronger 
tendency  to  alimentary  glycosuria,  which  sometimes 
affects  glucose  and  sometimes  laevulose  or  galactose. 
This  may  be  easily  explained  by  supposing  that  the 
damaged,  or  numerically  decreased,  liver  cells  cannot 
take  up  so  much  glycogen  as  in  times  of  health,  and 
that  therefore  more  sugar  passes  directly  from  the 
portal  vein  into  the  general  circulation.  It  is  only  the 
most  severe  diseases  of  the  parenchyma  of  the  liver 
which  seriously  disturb  sugar  formation.  This  hap- 
pens, for  instance,  in  acute  yellow  atrophy  and  phos- 
phorus poisoning;  but  the  actual  disturbances  which 
these  bring  about  in  the  elaboration  of  carbohydrates 
are  at  present  obscure.  Perhaps  they  are  confined  to 
total  inability  to  store  up  glycogen.  In  other  condi- 
tions it  is  surprising  with  what  tenacity  the  liver  clings 
to  its  controlling  function  in  spite  of  severe  disease. 
Assuredly  this  extraordinary  power  of  resistance  is  no 
chance  occurrence.     We  must  regard  it  as  an  impor- 


NEW  ASPECTS  OF  DIABETES  49 

tant  acquisition  in  the  struggle  for  existence.  Were 
it  otherwise,  and  were  every  disease  of  the  Hver  to  im- 
pair its  power  of  sugar  production,  the  continuance  of 
Hfe  would  be  threatened,  as  muscular  work,  and  still 
more  the  work  of  the  heart  cannot  go  on  without  the 
production  and  supply  of  sugar. 

B.  The  Influence  of  Other  Organs  on  the  Liver 

I  have  remarked  that  the  sugar  factory  does  not  de- 
pend entirely  on  the  degree  of  excitability  of  the  liver. 
Two  guards  are  set  over  the  liver  which  influence  its 
excitability  and  whose  forces  are  normally  equally 
balanced. 

a.  The  Pancreas 

7 

One  guard  is  the  pancreas ;  it  acts  as  a  breat.  to  the 
sugar  factory.  As  was  first  shown  by  your  own  coun- 
tr)mian,  Opie,  it  is  probably  the  so-called  islands  of 
Langerhans  which  liberate  the  active  stuff  into  the 
portal  blood.  When  the  pancreas  is  removed,  or  when 
the  islands  of  Langerhans  are  atrophied,  this  inhibitory 
action  fails.  The  excitability  of  the  sugar  factory  is 
enormously  raised ;  the  control  no  longer  exists  which 
equaHzes  sugar  production  to  sugar  requirements; 
more  sugar  is  formed  than  is  wanted.  The  blood  is 
flooded  with  it,  and  valuable  material  escapes  in  the 
urine.  In  experimental  pancreatic  diabetes  and  in  se- 
vere diabetes  in  man  the  liver  is  always  found  to  be 
free  from  glycogen.  This  may  be  explained  in  vari- 
ous ways : 


50         DISORDERS   OF   METABOLISM    AND   NUTRITION 

1.  The  absence  of  glycogen  depends  on  the  over 
excitabiHty  of  the  sugar  factory.  Even  in  health  gly- 
cogen is  the  least  stable  of  substances,  and  is  converted 
into  blood  sugar  more  easily  than  any  other.  Absence 
of  glycogen  in  the  liver  springs  from  increased  sugar 
production  in  pancreatic  diabetes,  just  as  it  does  in 
healthy  animals  when  exhausted  by  muscular  work; 
only  with  this  difference,  that  in  an  animal  at  work  the 
large  amount  of  sugar  formed  is  required  and  used  by 
the  tissues,  whereas  in  pancreatic  diabetes  the  absence 
of  impediment  allows  a  high  sugar  production  which 
is  absolutely  useless.  In  this  connection  we  must  re- 
member that  it  is  possible  to  furnish  the  liver  with  a 
certain  amount  of  glycogen  in  spite  of  pancreatic  dia- 
betes, by  using  Isevulose.  Recent  work  has  established 
the  hypothesis  which  I  put  forward  a  long  time  ago, 
that  laevulose-glycogen  is  not  identical  with  dextrose- 
glycogen.  The  former  has  shown  itself  much  more 
resistant  to  all  attacks  on  the  glycogen  stock  of  the 
liver.  Different  names  have  been  given  to  these  two 
glycogens  —  dextrogen  and  fructogen.  Unfortu- 
nately, we  can  only  make  small  therapeutic  use  of  this 
observation,  which  is,  however,  most  interesting  the- 
oretically. This  is  because  the  differences  almost  com- 
pletely disappear  after  Isevulose  has  been  given  for  any 
length  of  time. 

2.  The  second  explanation  of  the  absence  of  glyco- 
gen in  the  liver  is,  that  owing  to  the  failure  of  the 
internal  secretion  of  the  pancreas,  the  organ  loses  the 
power  of    forming  and  storing  glycogen.     Naunyn 


NEW    ASPECTS    OF    DIABETES  5 1 

coined  the  word  "  dyszoamylia  "  for  this  condition,  and 
saw  in  it  the  intrinsic  virtue  of  the  disease  known  as 
diabetes.  In  my  earher  pubHcations  in  New  York,  I 
have  tried  to  refer  some  of  the  metaboHc  disturbances 
in  diabetes  to  this,  for  their  orginal  cause.  You  see 
where  the  difference  between  these  two  conceptions 
lies.  In  the  first,  the  absence  of  glycogen  is  the  result 
of  increased  sugar  production,  and  in  the  second  it  is 
its  cause. 

Probably  it  is  not  correct  to  place  one  theory  in 
antagonism  to  the  other.  There  are  many  reasons  for 
believing  that  many  factors  unite  in  producing  a  single 
result  —  namely,  the  absence  of  glycogen  in  the  organs. 
One  factor  is  a  prodigality  in  sugar  production,  with 
the  result  of  impoverishing  the  glycogen  reserves  in 
the  liver;  the  other  is  a  specific  stimulation  of  the  dia- 
static  processes,  which  involves  not  only  the  liver,  but 
the  muscles  also. 

b.  The  Chromaffin  System 

We  must  pass  on  to  consider  the  relation  of  the 
suprarenals  and  the  rest  of  the  chromaffin  system  to 
sugar  production.  The  suprarenals  constitute  the  sec- 
ond of  the  guards  placed  over  the  liver  which  regulate 
the  excitability  of  the  sugar  factory.  Its  influence,  in 
contradistinction  to  that  of  the  pancreas,  is  one  of  stim- 
ulation. Adrenalin  causes  a  rapid  expulsion  of  glyco- 
gen from  the  liver ;  the  blood  is  flooded  with  sugar,  and 
glycosuria  results.  The  blood  sugar,  on  the  other 
hand,  falls  markedly  (to  0.5  per  mille  and  below)  after 


'52        DISORDERS   OF   METABOLISM   AND   NUTRITION 

extirpation  of  the  suprarenals,  and  in  severe  cases  of 
Addison's  disease.  A  moderate  dose  of  adrenalin  pro- 
duces a  glycosuria  lasting  for  some  hours.  After  that, 
normal  conditions  are  restored.  A  second  injection  of 
adrenalin  soon  afterwards  again  produces  glycosuria. 
But  if  the  injection  is  repeated  several  times,  gly- 
cosuria does  not  reappear,  but  only  moderate  hypergly- 
C3emia.  A  much  larger  dose  of  adrenalin  is  required 
to  produce  again  sugar  in  the  urine.  As  the  pancreas 
and  the  suprarenals  can  be  regarded  as  antagonistic  in 
their  action  on  the  liver,  the  inhibition  of  the  action  of 
adrenalin  may  be  explained  by  supposing  that  the  pan- 
creas was  taken  by  surprise  by  the  first  stimulating 
doses  of  adrenalin,  and  consequently  could  not  prevent 
the  disturbance  of  sugar  control.  But  the  repetition  of 
the  stimulus  puts  the  pancreas  into  a  strong  defensive 
condition.  Its  inhibitory  influence  makes  itself  felt, 
and  a  stop  is  put  to  the  disturbance  in  the  regulating 
mechanism  produced  by  the  adrenalin.  It  is  probable 
that  a  similar  intensification  of  the  pancreatic  functions 
also  accounts  for  the  fact,  that  in  conditions  of  chronic 
overaction  of  the  suprarenals,  such  as  we  so  often 
meet  with  in  hypertonic  arteriosclerosis  and  granular 
kidney,  there  is  no  glycosuria,  but  at  most  a  moderate 
hyperglycsemia.  Possibly,  too,  another  hitherto  unex- 
plained clinical  phenomenon  is  connected  with  this.  All 
of  you  know  of  cases  of  diabetes  which  have  gone  on 
for  a  long  time,  and  then,  on  the  development  of 
chronic  granular  kidney,  get  much  better  or  clear  up 
completely.     We  find  that  marked  hypertension  and 


NEW   ASPECTS   OF   DIABETES  53 

hypertrophy  of  the  heart  are  much  more  usually  pres- 
ent in  these  cases  than  in  other  forms  of  granular  kid- 
ney. The  blood  also  is  richer  in  adrenalin.  The  ad- 
renalin not  only  whips  up  the  liver,  but  also  the  pan- 
creas, causing  it  to  hyperactivity,  perhaps  especially  to 
hypertrophy  of  the  still  unhurt  activating  islands  of 
Langerhans.  Of  course,  there  is  much  in  this  explana- 
tion which  is  hypothetical ;  but  I  think  it  is  more  profit- 
able to  rely  upon  a  theory  for  what  it  is  worth,  and  to 
make  it  the  basis  for  further  studies,  than  to  content 
myself  with  the  meaningless  expression,  "  acquired  tol- 
erance of  adrenalin."  Let  us  next  see  what  patholog- 
ical anatomy  has  to  say.  We  must  see  whether,  in  cases 
of  simple  hypertension,  of  hypertonic  nephritis,  and  of 
post-diabetic  and  vascular  kidney,  hypertrophy  of  the 
islands  of  Langerhans  occurs.  This  must  be  specially 
looked  for  in  cases  where  there  has  been  hypergly- 
caemia  without  glycosuria  during  life.  Such  cases  are 
not  rare.  The  hypothesis  also  stimulates  us  to  thera- 
peutic experiments. 

So  far  as  the  liver  is  concerned,  the  injection  of  ad- 
renalin causes  rapid  expulsion  of  glycogen;  the  expres- 
sion is  often  used,  '*  adrenalin  mobilizes  glycogen."  No 
glycosuria  is  produced  by  small  doses  of  adrenalin,  if 
the  liver  is  previously  rendered  free  of  glycogen ;  larger 
doses,  however,  stimulate  the  whole  mechanism  of 
sugar  production.  They  produce  glycosuria  in  ani- 
mals which  have  been  freed  from  glycogen  by  starva- 
tion. Proteins  or  fats  must  therefore  be  employed  for 
the  formation  of  sugar.     When  the  inhibitory  action 


J54         DISORDERS   OF    METABOLISM    AND   NUTRITION 

of  the  pancreas  fails,  as  in  extirpation  of  the  pancreas 
and  in  severe  diabetes  in  man,  the  liver  is  especially 
susceptible  to  stimulation  by  adrenalin.  Quite  small 
doses,  which  would  be  inoperative  in  healthy  persons, 
send  up  the  sugar  excretion  by  leaps  and  bounds.  This 
fact  illustrates  most  beautifully  the  antagonism  be- 
tween the  two  glands,  as  it  shows  how  one  obtains  a 
predominance  as  soon  as  the  other  is  excluded.  But 
the  pancreas  and  the  chromaffin  system  have  not  the 
supreme  control  of  the  hepatic  sugar  production. 
Their  power  of  action  can  be  influenced  by  remote 
organs. 

c.  The  Nervous  System  —  Neurogenous  Diabetes 

The  chromaffin  system  is  the  one  in  which  this  is 
most  clearly  shown.  It  is  undoubtedly  under  the  in- 
fluence of  the  nervous  system.  It  has  been  shown  in 
Professor  H.  Meyer's  laboratory  in  Vienna  that  the 
nervous  influence  passes  down  by  way  of  the  left 
splanchnic  nerve  to  the  left  suprarenal  and  from  thence 
is  carried  across  to  the  right  one.  Stimulation  of  the 
sympathetic  mobilizes  the  adrenalin,  and  this  then  in- 
creases the  sugar  production  in  the  liver.  Claude  Ber- 
nard's famous  experiment  of  the  "  piqure "  demon- 
strates the  same  thing.  The  stimulation  of  the  medulla 
oblongata  is  passed  on  to  the  suprarenal  by  the  sympa- 
thetic. Piqiire  glycosuria  is  nothing  else  than  adrenalin 
glycosuria.  Claude  Bernard's  center  can  undoubtedly 
be  excited  not  only  by  gross  mechanical  lesions  but 
also  by  numerous  stimuli  of  psychical  and  somatic 


NEW  ASPECTS  OF  DIABETES  55 

origin.  We  now  understand  why  and  how  it  is  that 
certain  excitable,  nervous  individuals  can  exhibit  tran- 
sitory nervous  glycosuria  after  mental  or  physical  pain 
and  the  like.  We  understand  why,  in  true  diabetes, 
the  intensity  of  the  glycosuria  is  so  very  dependent  on 
the  condition  of  the  entire  nervous  system:  why  psy- 
chical stimuli,  mental  or  bodily  overstrain,  loss  of  sleep, 
etc.,  are  often  so  certain  to  set  up  glycosuria.  The 
same  process  is  again  set  going :  passage  of  the  stimulus 
to  the  center  in  the  medulla,  its  transference  through 
the  sympathetic  to  the  suprarenals,  mobilization  of  the 
adrenalin,  an  increased  sugar  production.  Investiga- 
tions in  my  clinic  by  Dr.  H.  Eppinger,  have  shown  that 
individuals  exist  with  a  highly  strung  vagus  system, 
and  others  in  whom  it  is  entirely  outweighed  by  the 
tonus  of  the  sympathetic  system  which  antagonizes 
it.  We  can  show,  that  those  with  a  highly  strung  sym- 
pathetic system  are  much  more  sensitive  to  adrenalin, 
and  exhibit  a  quite  considerable  glycosuria  after  even 
one  milligram  of  adrenalin;  whereas  those  with  a 
highly  strung  vagus  system  have  to  take  much  larger 
doses  to  produce  the  same  result.  Generally  speaking 
the  vagus  system  predominates  in  hysterical  persons, 
and  the  sympathetic  in  neurastheniacs.  We  also  find 
the  vagal  and  sympathetic  types  among  diabetics  and 
we  may  expect  that  stimuli  of  the  most  varied  kind  will 
excite  more  easily  through  the  sympathetic  nerves  and 
so  reach  the  suprarenals  and  increase  diabetic  gly- 
cosuria in  the  latter  class  than  in  the  former.  A  pre- 
liminary list  of  the  nervous  constitutions  of  our  dia- 


56         DISORDERS   OF    METABOLISM    AND   NUTRITION 

betics,  and  especially  as  regards  their  response  to  vago- 
tropic and  sympatheticotropic  drugs,  has  confirmed  the 
correctness  of  this  explanation.  When  we  remember 
that  in  the  large  majority  of  persons  the  tonus  of  the 
autonomic  and  sympathetic  nervous  systems  are 
equally  balanced,  and  that  it  is  only  in  a  minority  that 
the  one  outweighs  the  other  to  any  great  extent,  we 
shall  easily  see  that  the  same  nervous  stimulus  will  not 
always  produce  the  same  effect  on  the  diabetic  patient. 
There  are,  in  fact,  diabetics  whose  glycosuria  is  ex- 
traordinarily unaffected  by  any  kind  of  nervous  excite- 
ment, and  others  in  whom  the  glycosuria  is  in  the  high- 
est degree  sensitive  to  all  sorts  of  nervous  stimuli. 
And  between  these  two  classes  come  many  transitional 
forms.  We  must  now  deal  with  a  cognate  question, 
namely  whether  the  facts  already  ascertained  are  indic- 
ative of  the  existence  of  a  true  neurogenous  diabetes. 
In  my  opinion,  they  are  not.  I  think  we  can  only  say 
at  present  (i)  that  there  is  a  transitory  non-diabetic 
glycosuria  or  nervous  origin;  and  (2)  that  true  diabetic 
glycosuria  may  be  temporarily  increased  by  nervous 
influence.  It  is  quite  another  question,  whether  con- 
tinuous and  progressive  irritation  either  in  the  sympa- 
thetic nervous  system  or  in  the  suprarenals  can,  by  the 
exclusion  of  the  pancreas,  set  up  a  chronic  diabetes  in 
man.  In  this  connection  we  must  remember  that  long- 
continued  neurogenous  glycosuria  implies  long-con- 
tinued excess  of  adrenalin  in  the  blood.  The  blood  of 
diabetics  has  many  a  time  been  examined  for  excess  of 
adrenalin.     This  has  often  been  done  in  my  clinic, 


NEW  ASPECTS  OF  DIABETES  57 

but  always  with  negative  results.  We  only  know  of 
one  disease  in  which  excess  of  adrenalin  certainly  ex- 
ists, namely,  the  hypertonic  form  of  granular  kidney, 
and  this  is,  as  we  have  said,  to  a  certain  extent  antago- 
nistic to  diabetes  mellitus.  We  know  moreover  from  ex- 
periment that  it  is  only  a  sharp,  sudden  poisoning  with 
adrenalin  which  causes  glycosuria;  rapid  and  consid- 
erable increases  in  dosage  are  required  in  order  to  pro- 
long it.  We  have  suggested  that  this  is  due  to  a  com- 
pensatory stimulation  of  the  pancreas.  Experimen- 
tally, no  chronic  adrenalin-glycosuria  is  known.  From 
all  we  know  of  adrenalin,  it  is  certain,  that  chronic 
overaction  of  the  suprarenals  must  very  soon  become 
manifest  in  serious  changes  in  vascular  system.  But 
there  is  no  indication  of  this  in  those  young  or  middle- 
aged  people  in  whom  *'  neurogenous  diabetes  *'  is  most 
frequently  diagnosed.  Clinical  observation,  also,  tells 
against  the  existence  of  a  chronic  neurogenous  dia- 
betes. First,  the  glycosuria  must  be  shown  to  be  en- 
tirely independent  of  alimentary  conditions.  Now 
there  are  cases  of  diabetes  which  are  so  slight  that  at 
first  they  seem  independent  of  diet.  When  they  occur 
in  persons  with  a  very  excitable,  highly  strung  sympa- 
thetic nervous  system,  the  glycosuria  may  at  first  only 
appear  when  the  mechanism  for  sugar  formation  hap- 
pens to  be  damaged  by  nervous  influence.  More  accu- 
rate tests,  and  especially  long  and  careful  clinical  ob- 
servation will,  however,  make  clear  the  alimentary  fac- 
tor in  the  glycosuria.  Let  us  follow  these  cases  a  little 
further.     Year  by  year  the  hope  that  they  are  of  nerv- 


58         DISORDERS   OF    METABOLISM    AND    NUTRITION 

ous  origin  and  can  be  cured  by  placing  the  nervous 
system  under  favorable  conditions  becomes  less  and 
less  in  nearly  all  instances ;  finally  the  sad  conclusion  is 
reached  that  the  original  diagnosis  of  "  neurogenous 
diabetes  "  v^as  premature  and  false.  In  the  course  of 
the  last  twenty  years  I  have  had  under  clinical  treat- 
ment more  than  4,000  diabetics.  Moreover,  I  have 
seen  most  of  the  patients  again  and  again,  year  after 
year,  so  that  I  could  estimate  all  the  factors  controlling 
their  glycosuria.  Among  this  large  number  of  dia- 
betics there  are  hardly  twenty  whose  glycosuria  was 
permanently  independent  of  alimentary  conditions;  but 
on  the  other  hand  there  are  many  whose  diabetes  re- 
mained for  a  long  time  but  slightly  developed  and  in  a 
quite  harmless  stage ;  owing  to  rational  and  systematic 
diabetic  treatment.  In  these  cases  sugar  only  reap- 
peared in  the  urine  owing  to  careless  neglect  of  dia- 
betic rules,  or  severe  nervous  excitement.  There  are, 
however,  many  cases  in  which  from  the  beginning  the 
nervous  factor  in  the  glycosuria  appeared  to  predom- 
inate so  strongly  that  in  spite  of  every  care  and  the 
conscientious  observance  of  instructions,  day  by  day 
and  year  by  year  the  characteristic  picture  of  diabetes 
developed.  I  have  given  a  short  account  of  the  details 
of  a  most  instructive  case  of  this  kind  in  another  place 
{Medisinische  Klinik,  ipi2,  No.  i). 

When  we  discuss  therapeutics  we  shall  once  more 
briefly  revert  to  this  question.  In  the  meanwhile  I  feel 
bound  to  say  that  the  practical  physician  ought  to  be 
extremely  cautious  in  diagnosing  "  neurogenous  dia- 


NEW  ASPECTS  OF  DIABETES  59 

betes,"  otherwise  he  will  not  attach  sufficient  impor- 
tance to  the  regulation  of  the  diet,  and  will  thus  throw 
away  the  only  means  by  which  cure  or  improvement 
may  be  attained,  or  at  any  rate  the  downward  prog- 
ress of  the  disease  be  postponed. 

As  in  the  case  of  the  suprarenals,  the  pancreas  is  to 
a  certain  extent  subject  to  outside  influences.  It  has 
not  yet  been  possible  to  trace  the  connection  with  the 
nervous  system,  but  there  is  much  to  be  said  for  the 
view  that  the  vagus  has  some  relation  to  the  internal 
secretion  of  the  pancreas,  just  as  it  controls  its  ex- 
ternal secretion.  The  experiments,  however,  are  diffi- 
cult and  inconclusive,  and  it  would  be  premature  to  give 
a  definite  opinion. 

d.  The  Thyroid  System 

In  the  second  place  we  must  mention  the  thyroid 
gland.  Here  we  are  in  no  doubt  whatever.  The 
thyroid  and  pancreas  have  antagonistic  actions,  the 
former  inhibits  the  excitability  of  the  latter.  The 
more  powerful  the  action  of  the  thyroid,  the  more 
marked  the  inhibition.  A  similar  action  can  be  ob- 
tained by  thyroid  feeding.  Glycosuria  can  be  invari- 
ably induced  both  in  man  and  animals  on  a  mixed  diet, 
the  time  of  its  appearance  being  merely  a  question  of 
the  amount  of  thyroid  given;  on  the  other  hand  it  is 
almost  impossible  to  set  up  glycosuria  in  animals  after 
extirpation  of  the  thyroid  or  in  human  beings  suffer- 
ing from  myxoedema,  as  the  functional  activity  of  the 
pancreas  is  increased  by  the  absence  of  thyroid  influ- 


60         DISORDERS   OF    METABOLISM    AND   NUTRITION 

ence.  Probably  the  parathyroids  also  stand  in  meta- 
bolic relationship  to  the  pancreas.  These  glands  have 
not  yet  been  sufficiently  studied,  and  the  only  thing  that 
can  be  said  is  that  the  extirpation  of  the  epithelial 
bodies  (parathyroids)  weakens  the  functions  of  the 
pancreas  and  favors  the  onset  of  glycosuria.  This 
then  is  an  antagonistic  action  to  that  of  the  thyroids. 

e.  Diagram  Illustrating  the  Regulation 

Two  years  ago  I  devised  a  diagram  to  illustrate  the 
metabolic  relationship  of  the  organs  which  I  have  de- 
scribed. 

The  dotted  lines  indicate  "  nervous  paths,"  the  con- 
tinuous lines  "  blood  paths  " ;  the  arrows  show  the  di- 
rection of  the  stimulus;  and  the  plus  or  minus  signs 
behind  them  show  whether  the  stimulus  increases  or 
inhibits  the  power  of  the  organ  which  is  influenced. 

Paths  I,  II  and  III. — The  normal  metabolism  of  the 
carbohydrates  is  concerned  only  with  Paths  I,  II  and 
III. 

Path  I  shows  that  material,  inciting  an  increased 
activity  of  the  sugar- forming  mechanism,  streams  up 
from  the  intestine  to  the  liver.  This  path  in  diabetes 
corresponds  to  the  "  alimentary  factor  "  in  glycosuria. 
We  can,  at  will,  control  the  stimuli  passing  up  by  this 
way.  The  conscientious  carrying  out  of  this  is  the 
aim  and  object  of  diabetic  cures. 

Paths  II  and  III  show  the  action  of  the  metabolic 
processes  as  a  whole.  Along  Path  II  are  transmitted 
the  requirements  of  the  tissues  (especially  the  muscles) 


NEW   ASPECTS   OF   DIABETES 


6i 


^<f/ 


LIVBR 


CHROMAFFIK 


^uSJRHjJT^ 


t 


PANCRE-A5 


INTESTINE- 


62         DISORDERS   OF    METABOLISM    AND   NUTRITION 

and  to  their  extent  corresponds  to  the  amount  of  sugar 
formed  and  exported  by  the  blood  (Path  III,  hepatic 
vein,  heart  and  arteries).  The  total  stimulus  trans- 
mittal by  Path  II  can  also,  to  a  certain  extent,  be  volun- 
tarily controlled.  It  can  be  diminished  by  excluding 
everything  which  markedly  increases  the  total  produc- 
tion of  calories  (such  as  heavy  muscular  work,  loss  of 
heat,  abundant  food,  high  protein  diet).  That  these 
are  the  factors  which  increase  the  production  of  cal- 
ories and  at  the  same  time  the  formation  of  sugar  has 
already  been  noted;  and  we  make  use  of  this  knowl- 
edge to  achieve  our  aims  in  the  treatment  of  diabetes. 

Paths  A  and  B. — By  these  paths  the  influences  are 
sent  from  the  two  most  important  and  powerful  con- 
trollers, which  govern  the  sugar  factory.  It  is  the 
path  sensitizing  suprarenals  (Path  A)  and  of  the 
calming  pancreas  (Path  B). 

Paths  a  and  b. — Along  these  two  paths  indicate  the 
active  influences  by  which  the  functions  of  the  con- 
trolling organs  can  be  increased  or  diminished.  Along 
Path  a  pass  the  nervous  impulses.  It  is  along  this  path 
that  the  piqure  of  Claude  Bernard  exerts  its  effect,  and 
psychical  disturbances  obtain  their  influence  over  the 
sugar  production  of  diabetes.  There  may  also 
exist  other  paths  which  influence  the  production 
of  adrenalin,  and  consequently  that  of  sugar  also.  I 
refer  to  the  over-activity  of  the  suprarenals  and  the 
hypertension  developed  in  chronic  nephritis.  But 
there  is  so  much  uncertainty  surrounding  this  and 
other  questions,  that  I  have  only  suggested  in  the  dia- 


NEW  ASPECTS  OF  DIABETES  63 

gram  the  possibility  of  other  paths  than  that  of  the 
sympathetic. 

Path  b  indicates  the  certain  relationship  between  the 
thyroid  and  the  pancreas.  As  you  see,  the  indicator  on 
this  path  carries  a  negative  sign  to  show  that  the  in- 
ternal secretion  of  the  pancreas  is  not  increased  but 
inhibited  by  the  thyroid.  A  path  from  the  parathy- 
roids to  the  pancreas  (b  ^)  is  also  shown  on  the  dia- 
gram. The  indicator  carries  a  positive  sign.  Up  to 
the  present  the  probabiHty  of  the  existence  of  this  path 
is  only  supported  by  certain  experimental  facts.  There 
is  no  clinical  evidence  for  it  in  diabetes.  It  is,  how- 
ever, only  of  subordinate  importance.  The  impulses 
passing  to  the  pancreas  from  the  hypophysis  cerebri 
appear  to  be  more  far-reaching.  I  may  refer  to  the 
extraordinary  frequency  of  diabetes  in  acromegaly 
compared  with  the  astonishing  tolerance  of  carbohy- 
drates shown  in  cases  of  fatty  degeneration  of  the  so- 
called  dystrophia  adiposo-genitalis  (Hypophysare 
Fettsucht).  The  influence  of  the  pituitary  gland  is 
identical  with  that  of  the  thyroid. 

Paths  a  and  b  are  secondary.  When  the  functions  of 
the  two  principal  organs  (pancreas  and  suprarenals) 
are  normal,  the  extent  of  the  stimuli  they  originate  is 
of  no  great  or  immediate  importance.  When,  how- 
ever, there  is  any  morbid  predisposition  (such  as  an- 
atomical changes,  functional  debility,  or  diminished  ex- 
citability of  the  pancreas,  or  increased  excitability  of 
the  suprarenals)  the  more  distant  organs  can  exert  a 
distinct  influence  on  sugar  production. 


64        DISORDERS   OF   METABOLISM   AND   NUTRITION 

C.  The  Diabetic  Hyperirritation  of  the  Sugar- 
Forming  Apparatus 

We  must  look  for  the  immediate  cause  of  the  over- 
production of  sugar  in  diabetes  in  the  morbid  over- 
excitability  of  the  sugar  factory  in  the  liver.  Under 
normal  conditions  of  excitability,  overproduction  never 
occurs,  although  the  demands  on  sugar  production 
change  enormously  from  hour  to  hour.  The  two 
guards  placed  over  the  sugar  factory,  the  pancreas  and 
the  suprarenals  ensure  an  accurate  regulation  under 
normal  conditions.  It  is  otherwise,  however,  when 
the  inhibitory  power  of  the  pancreas  falls  into  abey- 
ance, or  when  a  wave  of  adrenalin  stimulates  the  sugar 
factory.  What  must  now  happen  is  obvious.  Every 
stimulus  which  under  such  circumstances  acts  on  the 
sugar  factory,  and  excites  it  to  sugar-production,  pro- 
duces abnormally  large  oscillation  in  the  regulatory 
mechanism.  The  amount  of  sugar  formed  and  passed 
on  into  the  blood  stream  is  now  not  merely  that  which 
is  required  by  the  tissues  and  can  be  oxidized  by  them, 
but  an  excessive  amount  is  produced  by  the  uncon- 
trolled mechanism  which  the  tissues  cannot  take  up  im- 
mediately. This  excess  remains  in  the  blood  and  is 
the  source  of  glycosuria.  Owing  to  the  overexcita- 
bility  of  the  sugar  factory  the  due  proportion  between 
the  strength  of  the  stimulus  and  its  effect  is  not  main- 
tained. The  disproportion  between  these  two  values 
—  the  stimulus  and  the  effect  —  also  determines  the 
severity  of  the  diabetes.     Thus  great  differences  in 


NEW  ASPECTS  OF  DIABETES  65 

degree  occur.  There  are  cases  in  which  the  sugar  fac- 
tory when  only  slightly  charged,  works  in  quite  a  nor- 
mal manner,  and  the  control  only  breaks  down  when 
the  sugar  factory  is  greatly  overcharged.  On  the 
other  hand,  there  are  cases  when  the  least  stimulation 
at  once  leads  to  the  overproduction  of  sugar.  All  in- 
termediate grades  are  also  found  in  the  pathology  of 
diabetes. 

Referring  to  our  diagram  we  should  say:  In  dia- 
betes, sugar-production  is  not  solely  controlled  by  the 
impulses  passing  along  Paths  I  and  II  as  in  health,  but 
the  condition  of  the  sugar-forming  organ  is  altered. 
Its  reaction  to  centripetal  impulses  is  increased;  it 
works  in  an  uncontrolled  and  wasteful  manner  and 
floods  Path  III  with  useless  material. 

You  see  that  I  explain  diabetic  glycosuria  as  entirely 
due  to  a  disproportion  between  the  strength  and  the 
effect  of  the  stimulus.  We  have  no  grounds  for  as- 
suming that  the  chemical  processes  which  lead  to  sugar 
formation  in  the  liver,  or  the  materials  from  which 
sugar  is  produced  are  qualitatively  otherwise  than  nor- 
mal Quantitatively,  however,  the  chemical  processes 
are  considerably  above  the  required  limit.  This  theory 
leaves  us  no  room  for  the  assumption  that  there  is  di- 
minished oxidation  of  sugar  in  the  tissues,  and  that 
other  materials  are  used  by  the  tissues  in  diabetics  in 
place  of  sugar,  which  streams  to  them  by  the  blood  in 
large  or  excessive  amounts.  I  must  here  point  out 
that  over-production  of  sugar  and  failure  to  oxidise 
sugar  are  two  quite  different  things. 


66         DISORDERS   OF    METABOLISM    AND   NUTRITION 

This  will  be  clearly  shown  by  means  of  a  little  dia- 
gram. 


Imagine  an  open  vessel,  filled  nearly  to  the  brim 
with  water.  It  has  an  escape  pipe  B,  through  which 
the  water  constantly  flows  out,  while  an  equal  quantity 
flows  in  at  the  supply  pipe  A.  Thus  the  surface  of  the 
water  always  remains  at  the  same  height.  If  the  con- 
ditions are  altered  and  the  vessel  overflows,  this  may 
be  due  to  several  things. 

Either  the  escape  pipe  has  got  blocked  so  that  the 
proper  amount  of  water  cannot  flow  away,  or  the  water 
flows  in  more  rapidly,  owing,  perhaps,  to  increased 


NEW  ASPECTS  OF  DIABETES  67 

pressure  in  the  supply.  Thus  two  quite  different 
causes  may  produce  the  same  result,  namely  the  over- 
flow of  the  vessel. 

Our  diagram,  of  course,  does  not  take  into  account 
the  details  of  the  biological  control. 

Explanation  of  the  Diagram 

The  vessel  —  the  blood. 

The  water  —  the  sugar  in  the  blood. 

The  supply  A  —  the   sugar  production  in  the  liver. 

The  escape  B  —  the    consumption    of    sugar    by    the 

tissues. 
The  escape  C  —  the  escape  of  the  excess  of  sugar  by 

the  kidneys. 

Of  course  theoretically  it  is  also  possible  that  the 
sugar  production  A  may  be  increased  and  at  the  same 
time  its  consumption  B  be  diminished.  If  this  is  as- 
sumed to  occur  in  diabetes,  we  must  be  quite  clear  in 
our  minds  that  we  are  assuming  the  co-existence  of 
two  entirely  different  functional  disturbances.  The 
seat  and  character  of  the  two  chemical  processes  are 
quite  different.  In  diabetes  we  can  only  be  certain  of 
the  disturbance  of  function  A;  all  the  experiments  de- 
signed to  find  positive  evidence  for  the  disturbance  of 
function  B  have  failed.  I  allude  to  the  theories  of 
R.  Lepine  and  O.  Cohnheim,  which  have  long  since 
been  abandoned.  On  the  other  hand,  in  the  observa- 
tions on  respiration,  after  the  portal  circulation  has 
been  cut  off,  we  have  positive  evidence  that  the  muscles 
can  oxidize  sugar  perfectly  well  even  when  the  pan- 
creas has  been  extirpated.  We  must  recognize  that  in 
order  to  maintain,  at  the  present  time,  the  existence  of 


68         DISORDERS   OF   METABOLISM    AND   NUTRITION 

defective  oxidation  of  sugar  in  diabetes,  entirely  new 
and  positive  evidence  must  be  produced. 

D.  Is  Diabetes  a  Single  Morbid  Entity? 

We  now  come  to  the  question  as  to  whether  we  are 
right  in  regarding  diabetes  as  a  single  morbid  entity. 
Under  the  imposing  impression  of  the  discovery  of  the 
"  pancreatic  diabetes  "  most  clinicians  and  pathologists 
trend  to  the  view  that  diabetes  is  caused  by  the  diminu- 
tion or  absence  of  the  internal  secretion  of  the  pan- 
creas, to  the  exclusion  of  other  concomitant  factors. 
If  we  once  more  glance  at  our  first  diagram  we  shall  see 
the  theoretical  objections  to  this  unitarian  doctrine. 
For  it  is  clear  that  the  irhpulses  coming  from  various 
parts  of  the  body  may  have  the  eventual  or  immediate 
effect  of  increasing  the  excitability  of  the  sugar  fac- 
tory. 

According  to  the  primary  anatomical  or  functional 
disturbances  we  have  to  distinguish 

Pancreas  diabetes  — 1 

Thyroid   diabetes  —J-    pancreatic  group. 

Hypophysis  diabetes  — J 


Suprarenal  diabetes  — 1  , 

- _  ^  ,.  ,   ^  y    suprarenal  group. 

Neurogenous  diabetes  — J 


To  a  great  extent  the  answers  to  these  questions 
must  be  left  to  the  future.  But  I  think  we  can  cer- 
tainly say  that  most,  if  not  all,  cases  of  really  chronic 
diabetes  must  be  referred  to  pancreatic  insufficiency. 


NEW  ASPECTS  OF  DIABETES  69 

Every  year,  more  delicate  histological  investigations 
bring  new  evidence  for  this  view.  This  was  first  of  all 
shown  in  cases  of  severe  diabetes;  for  exact  histolog- 
ical observations  on  the  pancreas  are  for  the  present 
very  scarce  in  those  extremely  frequent  cases  in  which 
some  final  complications  ended  a  long  period  of  slight 
glycosuria.  In  spite  of  the  extraordinary  variety  of 
the  course  of  the  disease  and  of  the  in- 
tensity of  the  glycosuria,  all  cases  of  diabetes  have 
one  point  in  common.  Including  the  very  slight 
and  the  quite  severe,  which  really  correspond  in  their 
principal  symptoms,  the  general  unity  of  type  in  all  is 
much  more  conspicuous  than  any  of  the  points  of  di- 
vergence. Some  authors,  especially  the  French,  are 
continually  seeking  to  introduce  new  schemes  of  class- 
ification in  diabetes.  How  artificial  and  far-fetched 
these  clinical  schemes  of  classification  seem!  The  di- 
visions are  purely  arbitary.  The  separation  of  such 
forms  as  diabete  maigre,  diabete  obese,  diabete  arthri- 
tique,  diabete  nerveux,  diabete  constitutionel,  diabete 
arteriosclerotique,  etc.,  has  only  setiological,  prognos- 
tic or  therapeutic  interest.  But  really  these  differenti- 
ations do  not  shake  the  essential  unity  of  the  metabolic 
disturbance  in  diabetes  in  the  very  least.  I  think  I 
shall  be  voicing  the  opinion  of  all  pathologists  when  I 
say,  that  every  individual,  who  has  a  diminished  tol- 
erance for  carbohydrates,  either  permanently,  or  ex- 
tending at  least  over  a  considerable  period,  and  thus 
exhibits  the  most  important  clinical  symptom  of  dia- 
betes, must  be  considered  as  a  subject  of  pancreatic  in- 


70         DISORDERS   OF    METABOLISM   AND   NUTRITION 

sufficiency.  We  need  not  always  expect  to  find  per- 
ceptible anatomical  evidence,  for  there  may  be  func- 
tional impairment  where  no  macroscopic  or  microsco- 
pic pathological  appearances  can  be  discovered. 

The  usual  share  taken  by  the  pancreas  in  exciting 
the  metabolic  disturbances  of  diabetes  is  in  full  agree- 
ment with  our  theory.  For  it  assumes,  that  a  healthy 
and  functionally  active  pancreas  is,  under  all  condi- 
tions, powerful  enough  to  make  its  inhibitory  action 
felt  on  the  sugar  factory.  Much  overfeeding  with 
sugar,  considerable  stimulation  of  the  sympathetic 
nervous  system,  acute  toxic  conditions  which  mobilize 
the  adrenalin,  etc.,  may  temporarily  exert  so  powerful 
an  exciting  influence  as  to  overcome  the  inhibitory  ac- 
tion of  the  pancreas.  Then  transitory,  non-diahetic 
glycosuria  occurs.  But  when,  in  any  particular  case, 
alimentary,  nervous  or  toxic  stimuli  which  would  not 
set  up  glycosuria  in  average  individuals,  always  pro- 
duce fresh  attacks  of  glycosuria,  we  must  assume  that 
somehow  the  inhibitory  action  of  the  pancreas  is  in- 
sufficient. It  is  quite  wrong  and  unscientific  to  adopt 
the  intensity  of  the  glycosuria  as  a  standard  whereby 
to  determine  whether  or  not  the  pancreas  is  involved. 
We  may  learn  this  from  the  course  of  those  cases 
which,  light  in  the  beginning,  in  their  later  stages  man- 
ifest all  the  most  severe  and  ominous  characteristics 
of  pancreatic  diabetes.  I  allude  to  those  cases  of  dia- 
betes in  children  which  every  doctor  regards  as  pancre- 
atic. All  who  have  seen  the  beginnings  of  these  cases 
know  that  in  the  early  months  they  appear  to  be  of  the 


NEW   ASPECTS   OF  DIABETES  7 1 

slightest  degree  imaginable.  Very  careful  investiga- 
tions show  the  presence  of  a  little  sugar  on  one  or  two 
occasions  only.  Many  controlled  tests  show  it  to  be 
completely  absent,  it  is  even  difficult  in  many  cases  to 
produce  sugar  excretion  even  by  unusually  large 
amounts  of  starchy  foods.  Thus  from  the  clinical 
standpoint  we  have  to  do  with  merely  a  very  slight 
transitory  glycosuria,  and  yet  anyone  who  knows  any- 
thing of  diabetes  is  aware  that  the  chances  are  that  at 
least  ninety  per  cent,  of  such  cases  will  in  another 
year  have  developed  into  hopelessly  severe  diabetes. 
In  children,  diabetes  is  nearly  always  progressive,  and 
all  that  treatment  can  do,  is  to  delay  the  advance  of 
the  disease.  In  the  diabetes  of  children  there  is  most 
usually  an  idiopathic,  progressive  atrophy  of  the 
islands  of  Langerhans.  In  adults,  other  inflammatory 
and  degenerative  changes  in  the  parenchyma  and  in- 
terstitial tissues  are  far  more  common.  Often  the 
process  remains  stationary  at  an  early  stage  of  its  de- 
velopment, or  retrogress;  or  the  disappearance  of  some 
groups  of  islands  is  compensated  by  the  hypertrophy  of 
others,  as  Weichselbaum  recently  showed.  Accord- 
ingly in  adults  we  very  often  meet  with  cases  which 
permanently  assume  a  very  slight  and  harmless  char- 
acter; this  appears  when  judicious  treatment  protects 
the  diseased  and  weakened  organ  from  becoming  over- 
taxed. But  there  is  no  reason  for  doubting  that  in 
these  cases  also  the  permanent  tendency  of  glycosuria 
is  closely  connected  with  pancreatic  insufficiency. 
The  more  completely  I  find  myself  in  agreement  with 


y2        DISORDERS  OF   METABOLISM    AND   NUTRITION 

the  views  of  Minkowski  and  all  the  other  exponents  of 
experimental  pathology  who  hold  that  in  all  cases  of 
chronic  diabetic  disturbance  of  metabolism,  pancreatic 
insufficiency  must  be  assumed  to  exist,  the  more  I  feel 
bound  to  insist  that  in  such  cases  all  the  other  factors, 
which  can  exert  a  direct  or  indirect  influence  on  sugar- 
production,  must  have  an  easier  part  to  play.  The 
most  potent  inhibitory  power  is  weakened,  or  in  the 
most  severe  cases  entirely  removed,  and  so  the  other 
factors,  which  are  essentially  excitant,  have  free  access 
to  the  sugar  factory.  Thus  in  diabetes  besides  the  ali- 
mentary factor,  the  other  exciting  impulses  from  the 
suprarenals,  the  nervous  system,  the  thyroids,  etc., 
make  their  effects  far  more  easily  felt.  Whether  this 
occurs,  and  to  what  extent,  depends  on  the  individual's 
constitution  and  the  presence  of  complications.  The 
most  varied  clinical  pictures  occur,  which  also  vary 
from  the  point  of  view  of  treatment  and  prognosis.  I 
allude  to  cases  complicated  by  neurasthenia,  Graves's 
disease,  acromegaly,  melancholia,  etc.  The  resulting 
clinical  pictures  are  easily  explained  by  a  reference  to 
our  diagram. 

The  analysis  of  the  endogenous  factors  which  are 
able  to  influence  sugar-production  do  not  by  any  means 
destroy  the  essential  unity  of  diabetes  in  man.  It  en- 
ables us,  however,  to  understand  more  clearly  the  man- 
ifold symptoms,  and  to  estimate  more  exactly  the  influ- 
ences which  so  often  dominate  the  increase  or  diminu- 
tion of  diabetic  glycosuria.  The  essential  unity  is 
maintained  by  our  constant  assumption  of  pancreatic 
insufficiency. 


IV.  THE  THERAPY  OF  DIABETES 

I  do  not  propose  to  mention  here  all  the  questions 
connected  with  the  therapy  of  diabetes  mellitus.  I  will 
limit  myself  chiefly  to  some  of  the  important  stand- 
points which  arise  from  the  considerations  already  ad- 
vanced, and  only  more  fully  deal  with  certain  questions. 
As  for  the  rest,  I  must  refer  you  in  part  to  my  earlier 
lectures  in  New  York,*  and  in  part  to  the  sixth  edition 
of  my  monograph  on  diabetes,  which  has  recently  been 
published   (Berlin.     A.  Hirschwald,  Publisher). 

A.  Introduction 

The  treatment  of  diabetes  has  been  restricted  to  cer- 
tain definite  lines  since  the  days  of  RoUo,  and  this 
limitation  is  but  now  being  extended.  Rollo  was  the 
first  to  discover  that  urinary  sugar  decreased  or  dis- 
appeared from  the  urine  when  sugar  and  mealstuffs 
were  excluded  from  the  dietary ;  he  found  also  that  the 
general  condition  of  the  patients  then  got  better.  In 
those  days  the  chemical  constitution  of  foodstuffs  was 
quite  unknown,  and  many  decades  passed  before  the 
various  articles  of  diet  were  analyzed.  To-day  we 
have  a  more  precise  knowledge  of  the  composition  of 
foods.  But  we  cannot  say  that  certain  foodstuffs  are 
suitable  for  diabetics  simply  because  of  their  chemical 
composition.     Such   hard   and    fast   chemical   figures 

*"  Diabetes   Mellitus,   Its    Pathological   Chemistry   and   Treat- 
ment," New  York,  E.  B.  Treat  &  Co.,  1905. 

n 


74         DISORDERS   OF    METABOLISM    AND    NUTRITION 

would  mislead  us.  Further  investigations  on  the  in- 
fluence of  the  individual  foodstuffs  revealed  new  and 
special  peculiarities  and  it  has  not  been  possible  to  ex- 
plain them  satisfactorily  either  from  our  knowledge  of 
their  chemistry,  or  our  experience  of  their  digestion 
and  assimilation.  There  was  also  the  Remarkable  fact, 
that  diabetics  could  often  assimilate  a  food  well  when 
it  is  given  singly,  but  badly  when  it  is  mixed  with 
others.  We  have  still  at  present  to  gain  much  more 
from  empiricism  and  clinical  experience  than  was 
thought  to  be  possible  at  the  time  when  the  subject  of 
food  chemistry  first  made  its  triumphant  entry. 

B.  What  is  the  Object  of  Carbohydrate  Restric- 
tion? 

In  spite  of  such  special  considerations  the  general  di- 
rection that  the  intake  of  carbohydrates  should  be  re- 
stricted or  excluded,  stands  to-day  in  the  foreground 
of  diabetic  therapy,  just  as  it  did  in  the  previous  cen- 
tury. It  is  perhaps  more  emphasized  than  heretofore. 
What  is  the  object  of  this  treatment? 

a.  Avoidance  of  Loss  of  Energy 

The  exclusion  of  carbohydrates  avoids  first  of  all 
loss  of  sugar  and  through  the  substitution  of  fat  we 
give  the  diabetic  patient  a  material  which,  owing  to  the 
special  character  of  his  diseased  functions,  he  cannot 
squander  so  easily.  Only  in  the  most  severe  cases 
does  a  sugar  loss  accompany  such  a  diet,  and  then  only 


NEW  ASPECTS  OF  DIABETES  75 

to  a  slight  degree.  The  patient  recovers  himself;  he 
gains  strength,  for  he  now  receives  a  diet,  which  he  can 
dispose  of  physiologically,  whilst  at  an  earlier  date  un- 
der conditions  of  excessive  sugar  production  he  dis- 
sipated and  lost  the  greater  part  of  its  nutritional  value. 
From  the  standpoint  of  general  nutrition  we  could 
confine  ourselves  upon  diminishing  the  intake  of  carbo- 
hydrates as  far  as  to  prevent  large  loss  of  sugar  and  we 
could  fill  up  the  gap  by  a  quantity  of  fat,  sufficient  to 
cover  the  energy  loss  and  to  satisfy  the  total  calorific 
requirements.  The  patient  then  remains  in  a  good 
state  of  nutrition  or  even  increases  his  body  weight. 
To  this  the  practitioner's  method  of  treatment  is  lim- 
ited in  the  great  majority  of  cases,  namely,  to  a  diminu- 
tion of  the  glycosuria  to  a  low  value  and  a  care  for  the 
general  nutrition.  The  physician  most  frequently  ad- 
vises his  patient  that  it  is  better  to  have  some  tenths  per 
cent,  of  sugar  in  the  urine,  with  a  daily  loss  of  a  few 
grams  of  sugar,  than  to  decrease  further  the  carbohy- 
drate intake.  I  do  not  know  if  this  is  an  average  med- 
ical opinion  in  your  country.  In  my  sphere  of  action  I 
have  found  it  to  be  generally  so.  The  basis  of  this 
practice  is  mostly  the  fear  of  acetonuria.  A  fear  of 
acetonuria  is,  however,  quite  needless  in  the  majority 
of  cases.  I  will  return  to  this  point  later.  Partly 
a  certain  degree  of  laziness  leads  to  that  method  of 
diabetic  treatment;  for  it  requires  a  great  deal  of 
care  and  trouble  to  induce  the  disappearance  of  the 
last  trace  of  sugar  from  the  urine.  I  believe  that  one 
would  take  much  more  trouble  to  attain  this  as  soon  as 


"]()        DISORDERS   OF   METABOLISM    AND   NUTRITION 

one  appreciates  clearly  the  advantages  that  would  ac- 
crue to  the  diabetic  patient  by  making  the  urine  abso- 
lutely sugar- free. 

h.  Prevention  of  Complications 

Diabetes  is  a  disease  which  is  especially  prone  to 
complications.     There  is  scarcely  another  chronic  con- 
dition which  is  associated  with  so  many  forms  of  com- 
plications, or  which  is  such  a  hindrance  to  the  favor- 
able issue  of  occasional  complications;  yet  there  is  not 
another  one  which  admits  of  being  influenced  so  favor- 
ably in  this  regard  as  does  diabetes  mellitus.     It  is  an 
old  and  yet  ever  new  experience  that  the  danger  of 
complications  may  be  remarkably  minimized  if  it  is 
found  possible  to  keep  the  urine  free  from  sugar.     Of 
course,  it  is  not  the  final  small  loss  of  sugar  which  con- 
cerns us,  but  the  reduction  of  the  hyperglycsemia.     All 
pathologists  agree  about  this.     Recently  this  view  has 
received    additional   confirmation.     We   have   always 
learned  that  the  hyperglycaemia  persists  so  long  as  the 
urine  contains  sugar.     Newer  and  more  delicate  meth- 
ods of  blood  analysis  have  made  this  more  certain; 
there  are  only  two  or  three  cases  in  which  this  has  not 
been  obtained,  and  we  cannot  explain  at  present  what 
other  factors  are  at  work.     We  have  learned  also, 
however,  that  as   a   rule   the  hyperglycaemia  persists 
much  longer  than  the  glycosuria.     After  the  urine  has 
been  freed  from  the  last  traces  of  sugar,  often  several 
weeks  elapse  before  the  blood  sugar  returns  to  its  nor- 
mal level.     If  one  does  not  ensure  that  the  urine  is  per- 


NEW   ASPECTS   OF   DIABETES  "JJ 

fectly  sugar  free,  but  allows  that  on  occasional  days  or 
even  from  time  to  time  during  a  few  hours  only,  sugar 
is  demonstrable  in  the  urine,  then  we  may  be  sure  that 
the  hyperglycsemia  has  not  disappeared  and  may  fur- 
nish the  cause  of  the  complications. 

If  we  turn  to  our  clinical  experience  for  an  indica- 
tion of  the  types  of  diabetes  in  which  complications 
most  frequently  occur,  we  are  reminded  that  it  is  by  no 
means  the  severest  and  most  malignant  cases  which  are 
so  attacked.  The  worst  cases  of  diabetes  progress  rap- 
idly and  death  occurs  before  complications  have  time 
to  develop.  Emaciation,  loss  of  energy,  and  diabetic 
auto-intoxication  are  the  most  prominent.  Much  more 
frequent  are  complications  as  furunculosis,  neuralgia, 
carious  teeth,  optic  neuritis,  etc.,  in  the  light  and  even 
very  light  cases.  The  glycosuria  has  continued  for 
some  long  time,  and  the  patients  had  satisfied  them- 
selves that  the  sugar  has  not  at  any  time  been  more 
than  \-i  per  cent,  and  sometimes  was  completely  ab- 
sent. If  in  these  slight  cases,  which  upon  a  fairly  lib- 
eral diet  remains  apparently  sugar  free,  we  examine 
the  urine  several  times  each  day  and  not  only  a  24 
hours'  mixed  sample,  we  shall  find  that  the  number  of 
absolutely  sugar-free  cases  is  considerably  diminished, 
and  we  shall  learn  that  at  certain  times  sugar  reappears 
in  the  urine.  The  same  patient  may  pass  urine  half- 
an-hour  later  which  again  is  quite  sugar- free.  I  have 
analyzed  the  blood  in  many  cases  of  this  kind.  Hyper- 
glycsemia  was  present  in  all  of  them. 

One  may  perhaps  wonder  how  it  is  that  in  spite  of 


78        DISORDERS   OF   METABOLISM   AND   NUTRITION 

the  hyperglycsemia,  the  glycosuria  is  inconsistent. 
This  depends  upon  special  renal  conditions,  a  fact 
which  I  called  attention  to  some  seven  years  ago;  the 
kidney  becomes  less  permeable  to  sugar  as  time  goes 
on.  While  at  the  beginning  of  the  disease,  glycosuria 
appears  when  the  sugar  content  of  the  blood  is  i  per 
mille,  later  on  the  urine  may  be  free  from  sugar,  al- 
though the  blood  control  has  reached  1.5  per  mille. 

I  consider  this  as  a  compensatory  mechanism  of  the 
organism  in  order  to  avoid  the  loss  of  sugar.  This 
fact  has  been  since  then  confirmed  by  many  observers. 
It  has  been  shown  also  that  the  relations  existing  be- 
tween hyperglycsemia  and  glycosuria  are  controlled  by 
other  factors,  but  an  explanation  is  as  yet  not  available. 
For  instance,  hyperglycsemia  is  present  in  febrile  con- 
ditions, yet  glycosuria  is  rare.  One  can  only  suppose 
that  here  the  cause  is  some  change  in  the  renal  filter. 

Let  us  return  now  to  a  consideration  of  the  compli- 
cations of  diabetes.  I  have  taken  an  active  interest  in 
the  forms  of  neuritis ;  they  seem  to  be  a  direct  heritage 
of  diabetes;  in  no  other  complication  is  it  so  easily  pos- 
sible to  trace  the  absolute  dependence  of  the  condition 
upon  the  course  of  the  underlying  disease.  Diabetic 
neuritis  exhibits  numerous  manifestations.  Fre- 
quently it  is  only  a  slight  pain  which  moves  about,  now 
in  the  arms,  shoulders,  muscles  of  the  breast,  back  or 
gluteal  region,  bones,  now  in  large  joints,  such  as 
shoulders  or  knees.  Very  often  there  is  pain  in  the 
calves  that  later  becomes  a  definite  cramp  at  night.  A 
favorite  seat  of  marked  sensibility  and  slight  pain  is 


NEW  ASPECTS  OF  DIABETES  79 

the  external  cutaneous  femoral  nerve  which  manifests 
paresthesia  and  neuralgia.  If  we  examine  diabetics 
carefully  from  this  standpoint,  we  shall  find  that  50 
per  cent,  at  least  of  all  diabetics  show  hypo-  or  hyper- 
esthesia of  this  region.  As  I  have  said,  these  sensory 
changes  are  often  "  wandering  "  in  type.  We  may 
call  them  "  dolores  vagi."  At  other  times  the  area 
affected  is  more  definitely  related  to  certain  nerve  tis- 
sues and  we  meet  with  a  definite,  although  not  very  se- 
vere, form  of  neuralgia  (sciatica,  lumbago,  inter- 
costal neuralgia,  brachial  neuralgia,  etc.).  This  dia- 
betic neuritis  exhibits  an  elective  character  in  that  it 
picks  out  the  sensory  fibers.  I  place  the  feelings  of 
pains  by  fatigue  in  the  same  category.  Somewhat 
rarely  the  motor  fibers  are  also  attacked;  the  nerve 
more  frequently  involved  is  the  crural  nerve;  then 
comes  the  axillary  and  the  oculomotor  nerves.  Of 
the  sensory  nerves,  the  optic  nerve  is  the  most  often 
affected.  This  is  often  not  noticed.  If  we,  however, 
examine  regularly  the  visual  fields  of  our  diabetic  pa- 
tients we  shall  be  surprised  to  find  how  often  there  is 
a  certain  contraction  of  the  visual  field,  in  some  cases 
for  all  colors,  in  others  for  individual  colors.  The 
ophthalmoscope  may  not  reveal  the  slightest  changes. 
These  are  characteristic  features  of  a  retrobulbar  optic 
neuritis. 

I  ought  here  to  point  out  that  these  above-mentioned 
sensory  disturbances  have  sometimes  led  to  inaccurate 
diagnosis.  For  months  or  years  the  patients  had  been 
treated   for  rheumatism  or  gout  with  restriction  of 


8o        DISORDERS   OF   METABOLISM   AND   NUTRITION 

meat  food,  and  the  application  of  electricity,  massage, 
baths  of  various  sorts,  and  more  recently  with  radium 
emanations.  A  certain  improvement  had  resulted,  but 
there  had  not  followed  any  permanent  healing  and 
prevention  of  recurrences.  Occasionally  the  urine  had 
been  tested  for  sugar;  none  had  been  found,  or  only 
traces,  and  these  had  disappeared  before  the  next  an- 
alysis. Therefore  one  had  rejected  the  diagnosis  of 
diabetes,  but  this  was  wrong.  One  had  rather  to  deal 
with  a  pure  diabetic  neuritis.  I  have  seen  many  hun- 
dreds of  such  cases,  and  am  able  to  state  that  in  every 
one  of  them  surprising  results  have  followed  a  well- 
directed  use  of  anti-diabetic  dietaries.  I  may  empha- 
size the  fact  that  complete  healing  of  the  troublesome 
symptoms  will  only  take  place  when  the  urine  is  quite 
freed  from  sugar ;  it  is  not  sufficient  simply  to  obtain  a 
diminution.  It  is  also  necessary  to  remember  that 
unless  the  hyperglycsemia  is  removed  the  troubles  will 
not  cease.  This  is  the  same  in  all  diabetic  complica- 
tions. In  diabetic  gangrene  it  is  especially  important 
to  attack  the  hyperglycsemic  condition.  We  are  often 
surprised  that  the  process  heals  so  slowly  in  spite  of  the 
fact  that  the  urine  is  free  from  sugar;  if  the  blood  is 
analyzed,  however,  the  explanation  will  be  quite  clear ; 
the  hyperglycsemia  has  not  disappeared  and  very  ener- 
getic treatment  will  be  found  necessary  to  effect  its 
removal.  Once  this  is  effected,  the  healing  will  pro- 
gress more  rapidly. 

You  see,  therefore,  that  the  carbohydrate  restriction 
and  the  substitution  of  other  nutritive  material  are  not 


NEW  ASPECTS  OF  DIABETES  8l 

alone  aimed  at  the  cessation  of  the  diabetic  glycosuria, 
but  the  same  measures  tend  secondly  to  avoid  possible 
complications  and  to  terminate  them  when  they  occur. 

c.  Treatment  of   the  Hyper  irritation   of  the  Sugar- 
Forming  Apparatus 

I.  Disadvantages  of  Carbohydrates. — Still  more  im- 
portant is  another  consequence  of  the  carbohydrate  re- 
striction. We  have  seen  that  in  diabetes  the  sugar  fac- 
tory is  in  such  a  high  state  of  excitability,  that  every 
stimulus  calls  forth  an  unduly  intense  reaction,  or,  to 
put  the  matter  in  other  words,  an  excessive  formation  of 
sugar  is  induced.  The  indications  are  to  obtain  rest  for 
the  overstimulated  organ,  to  decrease  the  overweighting 
of  the  regulating  factors  to  a  minimum  and  to  spare 
the  sugar  producing  organs  as  much  as  possible.  We 
utilize  the  same  principles  in  all  acute  and  chronic  dis- 
eases. When  a  leg  is  injured,  we  put  the  patient  to 
bed;  in  cardiac  diseases  we  forbid  bodily  overstrain 
or  undue  excitement;  in  anatomical  or  functional 
changes  in  the  stomach  we  select  a  form  of  diet  which 
will  give  the  organ  the  smallest  possible  amount  of 
work;  in  renal  disease,  food  is  chosen  which  contains 
a  minimum  quantity  of  material  which  may  damage 
the  renal  cells  during  elimination,  or  cause  extra  work 
to  be  thrown  on  the  kidney.  We  consider  that  by 
such  systematic  sparing  of  the  organs  we  are  putting 
them  into  the  best  circumstances  for  their  recovery  and 
return  to  normal  vigor.  Then  when  we  recognize  the 
signs  of  a  reappearing  health  and  activity,  we  endeavor 


S2         DISORDERS    OF    METABOLISM    AND    NUTRITION 

by  the  aid  of  carefully  graduated  work  to  accustom 
the  organ  to  its  usual  functions  and  to  prepare  it  for 
the  average  amount  of  doing.  This  all  appeals  to  us 
as  being  self-evident,  and  of  course,  v^e  ought  equally 
to  apply  the  same  principles  in  our  diabetic  therapy. 
As  a  rule,  however,  this  conception  does  not  obtain, 
and  where  it  does  it  is  usually  carried  out  in  a  half- 
hearted measure  only.  This  arises  from  the  nature 
of  the  disease.  With  affections  of  the  joints,  muscles, 
heart,  stomach,  etc.,  therapeutic  errors,  neglect  or  too 
rapid  return  to  work  of  the  damaged  organ,  are  at 
once  evident;  they  admonish  us  at  once  to  renewed 
care  and  vigilance.  In  diabetes,  however,  the  chief 
difficulty  lies  in  the  fact  that  the  danger  is  one  of  the 
future.  This  is  the  insidious  peculiarity  of  diabetes. 
We  do  not  at  all  disturb  for  the  present  the  general 
well-being  of  the  diabetic  if  we  treat  him  badly  and 
overweight  his  weakened  functions ;  yes,  we  may  even 
improve  by  psychical  influence  his  momentary  well 
being  if  we  permit  a  more  liberal  diet.  We  are,  how- 
ever, playing  a  dangerous  game.  We  are  thinking 
only  of  the  present  and  forgetting  the  future,  the  for- 
tunes of  which  depend  upon  the  vigilance  of  the  prac- 
titioner. If  we  allow  the  patient  suffering  from  renal 
disease  as  much  meat  and  sodium  chloride  as  a  healthy 
individual  can  take  each  day  without  hurt,  the  dam- 
aged kidney  is  stimulated  to  do  more  work;  we  in- 
jure it  further,  and  delay  the  recovery  of  the  portions 
which  can  yet  be  healed.  When  we  allow  the  diabetic 
to  take  whatever  quantity  of  carbohydrate  he  likes,  we 
commit  the  same  fault;  we  overweight  the  compensa- 


NEW   ASPECTS   OF   DIABETES 


83 


tory  powers  and  hinder  the  recovery  of  the  organs 
concerned.  Carbohydrates  act  upon  the  sugar  form- 
ing processes  more  intensely  than  any  other  irritant. 
When  the  carbohydrates  enter  the  Hver  they  set  the 
glycogen- forming  and  glycogen-destroying  processes 
in  full  swing.  We  see  that  carbohydrates  also  over- 
weight the  functions  concerned  with  the  regulation 
of  the  processes.  This  overloading  brings  about  an 
immediate  result,  namely,  an  overflowing  of  the  car- 
bohydrates into  the  blood  and  its  excretion  by  the 
urine.  But  it  does  not  stop  at  that.  It  is  quite  easy 
to  show  that  this  is  not  the  only  harm  which  follows 
too  great  an  intake  of  carbohydrate.  We  learn  this 
from  a  case  in  which  we  determined  a  diet  for  a  dia- 
betic patient  which  allowed  him  to  remain  sugar  free 
and  then  we  exceeded  the  bounds  of  tolerance.  It 
may  be  two  or  three  days,  or  even  a  longer  time,  be- 
fore the  damage  becomes  really  apparent.  I  append 
a  table : 

Day  Diet  Sugar  in  urine 

I  Restricted  +  2fo  gr.  Bread  o 


2 

a                  tc 

it 

0 

3 

(t                 (( 

it 

0 

4 

50 

it 

0 

5 

«                  (I 

« 

0 

6 

<e                  u 

« 

S2  gr. 

7 

((                  t( 

it 

12.7   " 

8 

20 

it 

11.3   " 

9 

It              « 

it 

8.2  " 

10 

(t                      U 

tt 

7.1   " 

II 

It               It 

tt 

4.9  " 

12 

<«               tt 

tt 

6.4  " 

13 

0- 

«_ 

0 

14 

20 

Bread 

0 

15 

«               It 

tt 

0 

84         DISORDERS    OF    METABOLISM    AND   NUTRITION 

The  patient  remained  sugar-free  so  long  as  the 
daily  intake  of  carbohydrates  did  not  exceed  20  grams 
of  bread.  In  order  to  see  if  he  could  be  allowed  more 
bread  the  amount  was  increased  to  50  grams  daily. 

On  the  first  two  days,  the  patient  took  the  50  grams 
of  bread  wonderfully  well;  there  was  not  a  trace  of 
sugar  in  the  urine.  The  third  day's  urine  contained 
a  small  amount,  the  fourth  day's  a  marked  glycosuria. 
yVe  returned  to  the  earlier  diet  at  once.  If  it  had  been 
only  the  excess  of  30  grams  of  bread,  the  organism 
was  not  quite  ready  for,  then  the  urine  upon  the  first, 
or  at  latest,  the  second  day  of  the  earlier  diet  would 
have  been  again  free  from  sugar;  the  small  quantity 
of  carbohydrates  present  in  the  slight  excess  of  bread 
is  naturally  rapidly  consumed.  But  here  we  have 
a  glycosuria  which  lasted  five  days  longer  and  the 
urine  only  became  free  from  sugar  when  we  left 
away  all  carbohydrates  one  day  long.  But  then  the 
urine  attained  the  same  freedom  from  sugar  as  at 
the  commencement  of  the  experiment.  The  example 
is  a  typical  one.  It  shows  something  that  we  can  see 
every  day;  I  could  bring  forward  hundreds  of  similar 
instances.  What  ought  we  to  learn  from  this?  We 
may  learn  that  we  saddled  the  liver  with  more  car- 
bohydrate than  it  could  deal  with,  and  also  brought 
about  upon  that  hypersensitive  organ  an  irritant  ac- 
tion, which  outlasted  the  primary  effect  and  only  dis- 
appeared when  we  allowed  the  irritated  organ  com- 
plete rest.  We  may  perhaps  sum  up  the  matter  in 
the   following  sentence:   Overworking  of  the  sugar 


NEW   ASPECTS   OF   DIABETES  85 

manufactories  in  diabetes  not  only  leads  to  an  im- 
mediate abnormal  increase  in  the  production  of  sugar, 
it  also  leaves  behind  an  increased  excitability. 

2.  Disadvantages  of  Large  Intakes  of  Albumin. — As 
m  the  case  of  carbohydrates,  so  in  that  of  large  al- 
bumin intakes  there  follows  an  increased  excitability 
of  the  sugar  forming  process,  although  much  depends 
upon  the  type  of  the  albumin.  The  extent  of  the  irri- 
tation is  less  than  that  of  the  carbohydrate.  This  has 
been  pointed  out  previously.  The  influence  of  the 
albumin  is  not  the  same  in  every  case,  however ;  a  cer- 
tain stage  of  the  disease  is  necessary  for  the  influence 
to  attain  any  importance.  This  was  so  in  the  follow- 
ing example:  The  patient's  urine  remained  free  from 
sugar  so  long  as  the  intake  did  not  exceed  70  grams 
of  albumin  and  as  long  as  large  amounts  of  green 
vegetables  and  fat  were  given.  To  this  diet  there 
was  added  200  grams  of  beefsteak  (raw  weight)  on 
two  successive  days.  Already  on  the  first  day,  sugar 
appeared  in  the  urine;  there  was  more  on  the  second 
day;  although  through  an  immediate  return  to  the 
first  diet  the  sugar  was  reduced,  the  glycosuria  failed 
to  disappear  for  four  days.     Here  also  there  was  a 

Day  Diet  Sugar  in  the  urine 

1  Meat,  eggs,  green  vegetables,   butter — containing 

70  gr.   of  proteids  o 

2  "  o 

3  "  0 

4  the    same    and    200    gr    beefsteak  5.2  gr. 

5  "  13.8    " 


86        DISORDERS   OF    METABOLISM   AND   NUTRITION 

Day  Diet  Sugar  in  the  urine 

6  the  same  as  on  the  I  to  III  day  d.^  gr. 

7  "  4.8  " 

8  "  3-2  " 

9  "  1.8  " 
10  "  0 

long  drawnout  effect  of  the  transitory  irritant.  You 
cannot  show  in  every  case  so  clearly  that  forced  work 
leaves  such  effects.  The  first  need  is  naturally  a 
proper  arrangement  of  the  dietary,  and  a  careful 
watch  over  the  patient.  Secondly,  it  may  happen  in 
many  cases,  especially  those  of  slight  diabetes,  that 
the  effects  appear  more  slowly  than  in  the  instance  we 
have  quoted.  Sometimes,  two  or  three  weeks  may  be 
necessary  before  we  clearly  see  that  we  overstrained 
the  power  of  the  sugar  factory.  This  peculiarity  of 
the  slighter  cases  makes  the  determination  of  the 
tolerance  factors  very  difficult,  and  may  lead  the  in- 
experienced worker  into  error. 

3.  Recovery  of  the  Sugar-Forming  'Apparatus.' — ■- 
When,  on  the  one  hand,  we  see  that  the  overworking 
of  the  sugar  factories  becomes  evident,  in  one  instance 
quickly  and  in  another  more  slowly,  but  that  in  all 
there  is  a  definite  progress  to  greater  excitation  of 
the  organs  and  disorder  of  the  regulating  functions, 
we  are  bound  to  observe,  on  the  other  hand,  that  the 
principles  of  the  calming  therapy  (Schonungs-therapie) 
are  the  only  ones  upon  which  the  best  and  most  satis- 
factory results  may  be  based.  Good  results  are  often 
obtained  within  a  short  time.  Sometimes  weeks  and 
months  are  necessary  before  a  satisfactory  effect  fol- 
lows.    [We  must  not  forget,  however,  that  in  many 


NEW   ASPECTS   OF  DIABETES  87 

other  cases  our  efforts  may  be  futile,  for  we  are  face 
to  face  with  a  chronic  disease  and  as  in  cardiac  condi- 
tions and  other  chronic  diseases  we  cannot  expect  too 
much. 

An  immediate  improvement,  However,  can  be  ob- 
tained in  every  case  of  diabetes  —  light  or  severe  — 
as  a  result  of  the  calming  treatment,  and  this  may  be 
demonstrated  quite  easily.  I  append  an  example  of 
this. 

The  patient  was  on  a  fixed  diet  which  contained  75 
grams  of  bread  in  addition  to  albumin,  fat  and  green 
vegetables;  you  will  see  that  there  was  an  average 
sugar  output  of  15  grams  daily.  Bread  was  then 
withdrawn  and  the  patient  put  on  a  carbohydrate  free 
diet  for  three  weeks.  The  sugar  soon  disappeared. 
We  then  added  bread  gradually,  and  every  third  day 
we  substituted  a  restricted  diet.  In  this  way  we  con- 
tinued until  we  reached  an  intake  of  80  grams  of  bread 
without  a  trace  of  sugar  appearing  in  the  urine. 
Through  this  form  of  calming  treatment  (Schonungs- 
cur)  the  tolerance  of  the  patient  was  improved  mark- 
edly in  a  very  short  time. 


Day 

Diet 

Sugar  in 

.  the  urine 

I     Restricted 

diet 

and   75   gr. 

bread 

158  gr. 

2 

(( 

« 

12.2 

3 

(( 

(( 

16.9 

4 

(t 

u 

14. 1 

5 

(C 

without  bread 

7.2 

6 

" 

" 

2.1 

7 

<t 

(( 

traces 

8-27 

(( 

•« 

0 

88        DISORDERS   OF   METABOLISM    AND   NUTRITION 


Day 

Diet 

Sugar  in  the  urme 

28 

Restricted 

diet  and  25  gr.  bread 

0 

29 

(( 

« 

0 

30 

(( 

without  bread 

0 

31 

(( 

and  35   gr.  bread 

0 

32 

tt 

(( 

0 

33 

(( 

without  bread 

0 

34 

(I 

and   50  gr.   bread 

0 

35 

(( 

« 

0 

36 

(I 

without  bread 

0 

37 

« 

and  65   gr.  bread 

0 

38 

(( 

(( 

0 

39 

(t 

without  bread 

0 

40 

" 

and   80  gr.   bread 

0 

41 

« 

a 

0 

4^ 

" 

without  bread 

0 

43 

(( 

and   80  gr.   bread 

0 

44 

tt 

tt 

0 

We  decided  further  that  the  patient  should  take  60 
grams  of  bread  daily,  but  that  once  each  week  there 
should  be  a  "  vegetable  "  day  on  which  not  only  the 
carbohydrate  should  be  cut  off,  but  the  albumin  re- 
duced to  a  minimum.  The  first  observation  dates  15 
years  ago.  Year  by  year  the  tolerance  of  the  patient 
has  improved  and  we  have  now  got  so  far  that  sugar 
appears  only  when  the  amount  of  bread  consumed 
exceeds  300  grams.  That  is  a  quantity  which  is  more 
than  the  average  intake  of  normal  men.  From  the 
practical  standpoint,  therefore,  we  may  consider  the 
patient  as  cured ;  this  is  the  more  remarkable  as  the  pa- 
tient was  25  years  old  when  the  malady  first  appeared 
—  an  age  pregnant  with  danger  for  a  diabetic  patient. 

I  could  bring  forward  many  similar  examples,  but 
I  think  that  I  have  said  sufficient  to  make  clear  the 


NEW  ASPECTS  OF  DIABETES  89 

principle  underlying  this  form  of  treatment.  I  have 
treated  personally  a  large  number  of  diabetics  and  I 
know,  in  the  majority  of  cases,  the  terminations  of  the 
condition.  The  wider  my  experience  got,  the  more  I 
learned  to  appreciate  the  enormous  importance  of  the 
benefits  attained  by  the  institution  and  carrying  out 
of  well  defined  restricted  dieting.  It  has  been  under 
these  conditions  alone  that  I  have  obtained  real  and 
permanent  improvement. 

C.  Principles  of  Treatment  in  Slight  Cases 

One  must  not  assume  that  every  case  of  diabetes 
necessarily  goes  to  the  bad.  There  are  some  cases 
which  do  not  show  any  progressive  tendencies  and 
only  become  worse  when  they  are  neglected  or  when 
there  is  allowed  an  always  repeated  excessive  excita- 
tion of  the  sugar  factory.  The  majority  of  these 
cases  are  among  those  just  over  50  years  of  age.  It 
is  well  known  that  the  prognosis  of  diabetes  in  gen- 
eral is  the  more  disastrous,  the  earlier  in  life  the  dis- 
ease commences.  Still,  there  are  many  diabetics  of 
middle  or  early  middle  life  in  which  a  favorable 
prognosis  is  permissible  and  decades  of  life  may  be 
predicted  provided  that  one  avoids  all  that  may  give 
the  disease  a  bad  turn. 

Of  course,  the  earlier  the  case  can  be  taken  in  hand 
the  better  it  will  yield  to  our  treatment.  We  must 
profit  by  the  period,  when  the  glycosuria  is  still  slight 
and  disappears  altogether  under  diminution  or  ex- 
clusion of  carbohydrate  food.     One  must  ensure  that 


90         DISORDERS   OF   METABOLISM    AND   NUTRITION 

this  be  a  permanent  disappearance  and  that  even 
transitory  reappearance  of  the  glycosuria  will  not  oc- 
cur. As  I  have  said  before,  I  think  that  this  aim 
mostly  is  not  fully  attained  and  that  not  enough 
v^eight  is  laid  upon  the  attainment,  because  one  is  more 
immediately  concerned  with  the  avoidance  of  large 
sugar  excretion,  and  does  not  remember  that  even  the 
slightest  trace  of  urinary  sugar  shows  that  the  sugar 
regulating  functions  are  overburdened  and  over-irri- 
tated and  that  the  sugar-excitation  of  an  already  de- 
fective function  must  lead  to  further  deficiences.  This 
is  the  more  to  be  deplored,  since  it  requires  but  slight 
restrictions  and  only  a  careful  regulation  of  the  diet- 
ary to  keep  the  urine  quite  free  from  sugar.  We  may 
perhaps  alter  a  French  proverb  to  fit  the  case  and  say 
"  Ce  n'est  que  le  dernier  pas  qui  coute.'' 

As  regards  the  question  of  diet,  the  all-important 
point  is  the  regulation  of  the  carbohydrate  and  protein 
supplies.  The  degree  to  which  the  carbohydrate 
group  in  general  or  individual  members  of  this  group 
in  particular  should  be  reduced,  must  vary  naturally 
in  every  case;  and  the  same  is  true  for  the  reduction 
of  the  protein  group  and  its  individual  members  as  an 
auxiliary  measure.  I  may  say  that  out  of  lOO  diabe- 
tics no  two  should  be  given  the  same  dietetic  prescrip- 
tions. As  a  general  rule,  the  slighter  the  case  and  the 
greater  the  hope,  that  by  avoiding  unnecessary  irrita- 
tion the  controlling  factors  may  be  brought  back  to 
health  and  strength,  the  more  strict  should  be  our 
regulations.     This  may  be  carried  out  with  more  coo- 


NEW   ASPECTS   OF  DIABETES  9 1 

fidence,  inasmuch  as  the  danger  of  acidosis  may  be 
entirely  excluded  in  these  slight  cases.  Transient 
acetonuria  may  easily  be  set  up  if  the  diet  is  rapidly 
changed,  but  dangerous  degrees  of  acetonuria  need 
not  be  feared.  When  finally,  after  a  considerable 
period,  a  threatening  degree  of  acidosis  occurs,  it  will 
be  found  that  the  glycosuria  is  also  markedly  worse. 
Then  the  acidosis  does  not  appear  as  a  result  of  the 
diminution  of  the  carbohydrates,  but  because  the  whole 
disease  is  becoming  worse  in  spite  of  the  precautions 
taken  against  it.  In  many  cases  this  is  the  inevitable 
course  of  events. 

D.  The  Principles  of  Treatment  in  Transitional 

Cases 

Contrariwise  to  my  practice  in  slight  cases,  I  am 
much  more  liberal  in  the  severer  ones;  more  liberal 
perhaps  than  the. majority  of  physicians.  In  every 
case,  I  do  indeed  at  first  try  to  render  the  urine  free 
from  sugar  by  cutting  out  the  carbohydrates  and  at 
the  same  time  reducing  the  proteins,  and  very  often 
by  employing  the  so-called  oatmeal  cure  as  an  addi- 
tional measure,  concerning  which  more  will  be  said 
later.  When  this  plan  is  carried  out  with  necessary 
care  and  attention  to  detail,  and  when  it  is  pursued  for 
a  sufficient  length  of  time,  it  is  surprising  how  often 
the  severe  form  of  glycosuria  can  be  converted  into  a 
slighter  form.  To  succeed  in  doing  this,  is  to  confer 
a  great  benefit  on  the  patient.     It  is  no  light  task. 


92         DISORDERS   OF   METABOLISM    AND   NUTRITION 

and  I  should  never  undertake  the  risks  of  carrying  out 
the  necessary  dietetic  measures  except  in  a  sanatorium 
for  dieting.  There  are  rocks  ahead  in  the  shape  of 
acetonuria  which,  though  undoubtedly  dangerous,  may 
be  avoided  if  foresight  is  used  in  directing  the  treat- 
ment. 

» 
E.  Principles  of  Treatment  in  Severe  Cases 

When  it  is  definitely  impossible  to  convert  a  severe 
diabetes  into  a  slight  one,  use  what  pains  and  care  as 
to  detail  we  may,  the  time  has  come  for  the  employ- 
ment of  milder  measures.  The  condition  is  one  of 
permanent,  irremediable  over-stimulation  of  the  sugar 
factory,  and  it  makes  little  difference  whether  the 
patient  excretes  20  or  30  grams  of  sugar  under  the 
very  strict  diet,  and  while  suffering  the  greatest  priva- 
tions, or  whether  he  excretes  50  to  60  grams  under  a 
careful  but  easily  tolerated  regimen.  In  the  latter 
case,  it  is  easier  to  secure  the  supply  of  a  sufficient 
total  of  calories,  as  large  quantities  of  fat  can  be  sup- 
plied with  the  prescribed  allowance  of  carbohydrates. 
On  the  other  hand,  I  consider  that  it  is  most  helpful 
to  make  an  occasional  break  in  the  liberal  dietary  by 
interposing  days  in  which  the  claims  on  the  sugar  fac- 
tory are  reduced  to  the  smallest  imaginable  dimen- 
sions. These  are  days  of  recuperation  for  the  sugar 
factory ;  indeed  they  are  the  Sundays  interposed  among 
working  days.  They  shall  do  for  the  sugar  factory 
what  Sundays  do  for  the  body  and  soul,  coming  in,  as 
they  do,  between  the  working  days  of  the  week. 


NEW  ASPECTS  OF  DIABETES  93 

Three  degrees  of  these  days  of  abstaining  may  be 
distinguished : 

(a)  Days  of  simply  strict  diet  —  that  is,  when 
carbohydrates  are  excluded. 

(b)  Days  of  vegetable  diet,  when  only  bacon,  but- 
ter and  a  few  eggs  are  taken  besides  green  vegetables. 

(c)  Fast  days,  in  which  only  weak  tea,  lemon 
squash,  or  whisky  and  soda  are  allowed.  On  such 
days,  I  am  in  the  habit  of  ordering  also  rest  in  bed 
to  reduce  the  total  production  of  calories,  and  thereby 
the  claims  made  on  the  sugar  factory,  to  the  smallest 
amount  imaginable.  There  are  but  few  diabetics 
who  do  not  become  sugar- free  on  these  days,  and  you 
will  at  the  time  notice  an  enormous  fall  in  the 
acetonuria.  Fast  days,  combined  with  bed  rest,  are 
excellently  borne.  I  never  find  that  the  patient's 
strength  is  unduly  diminished  by  them.  An  im- 
portant result  is  regularly  attained  in  the  immediate 
and  well  marked  rise  of  tolerance  which  follows. 

Of  course  it  is  only  by  taking  into  consideration  the 
special  conditions  of  each  case,  that  one  can  settle  how 
these  days  of  abstaining  are  to  be  distributed,  and 
whether  we  can  confine  ourselves  to  the  milder  varie- 
ties or  whether  we  must  occasionally  call  to  our  aid 
the  most  rigid  kind  —  namely,  the  single  days  of  fast- 
ing. Without  going  further  into  details,  I  will  now 
give  some  examples: 

I.    Example : 

6  days'  restricted  diet +  80  gr.  bread    (or  equivalents). 
I  day  restricted  diet  alone. 


94        DISORDERS   OF   METABOLISM   AND   NUTRITION 

5  days'  restricted  diet +  80  gr.  bread. 
I  day  vegetable-egg-day. 

The  same  scheme  begins  anew. 
II.    Example ; 

5  days'   restricted  diet -f- 60  gr.  bread. 
I  day  restricted  diet  alone. 

1  day   vegetable-egg-day. 

5  days*   restricted   diet +  60  gr.  bread. 

2  days'    vegetable-egg-days. 

The  same  scheme  begins  anew. 

III.  Example : 

5  days'   restricted  diet -|- 60  gr.  bread. 
2  days'  vegetable-egg-days. 

5  days'  restricted  diet  and  60  gr.  bread. 
I  day   vegetable-egg-day. 

I  day   fasting  day. 

The  same  scheme  begins  anew. 

IV.  Example : 

6  days'   restricted  diet  -\-  80  gr.   bread. 
I  day   vegetable-egg-day. 

6  days'   restricted   diet -f- 80  gr.   bread. 

I  day   vegetable-egg-day. 

5  days'    restricted   diet   alone. 

I  day  vegetable-egg-day. 

I  day  fasting  day. 

The  same  begins  anew. 

Many  other  combinations  are  possible  and  useful 
under  certain  circumstances.  As  increasing  experi- 
ence will  show  you,  that  in  the  severer  cases  the  toler- 
ance for  carbohydrates  will  be  improved  in  proportion 
as  the  protein  supply  is  diminished,  and  that  meat 
especially  must  be  reduced,  whereas  the  other  proteins 
need  not  be  diminished  to  the  same  extent.  The  pa- 
tient must  also  be  advised  to  take  large  quantities  of 
fat,  and  it  is  necessary  to  give  detailed  study  to  the 
form  and  amounts  in  which  the  fats  are  consumed,  in 
order  to  avoid  damage  to  the  digestive  organs. 


NEW  ASPECTS  OF  DIABETES  95 

F.  Tolerance  Determination 

If  ypu  do  not  wish^  as  it  were,  to  serve  a  ready- 
made  treatment  to  all,  but  consider  it  important  that 
each  patient  should  be  ordered  the  mode  of  life  and 
form  of  diet  which  is  most  suitable  to  his  individual 
case,  you  will  have  to  undertake  very  minute  investi- 
gations. This  is  true  of  the  slight  as  well  as  of  the 
severe  cases.  I  might  even  say  that  it  is  of  more  im- 
portance in  the  sHghter  cases  than  in  the  more  serious, 
as  in  the  former  there  is  more  to  be  gained  by  correct 
dietetic  rules  and  more  to  be  lost  by  wrong  ones. 

These  tests  I  have  called  the  '*  estimation  of  toler- 
ance." They  were  first  made  by  R.  Kuelz  in  Mar- 
burg, and  served  him  as  the  basis  of  an  individualistic 
treatment  of  diabetes.  I  have  further  extended  his 
methods,  and  adapted  them  to  the  modern  scientific 
conceptions  of  dietetics.  The  whole  of  modern 
diabetic  therapy  is,  however,  based  on  the  principles 
for  which  Kuelz  contended.  Before  then  there  was 
only  a  hard  and  fast,  superficial  treatment,  which  took 
no  account  of  the  variety  of  clinical  pictures  seen  in 
the  disease.  Kuelz  took  the  diabetic  into  his  private 
clinic,  and  tested  him  until  he  had  found  the  method 
of  dieting  which  gave  the  best  results  in  that  particular 
case.  Many  control  tests  were  made,  at  least  once  in 
twelve  months.  Kuelz  has  now  been  dead  for  seven- 
teen years.  The  greater  number  of  his  patients  came 
under  my  care  later  on,  and  it  is  a  brilliant  proof  of 
the  fruit  fulness  of  his  methods,  that  I  now  have  many 


96         DISORDERS   OF   METABOLISM    AND   NUTRITION 

patients  still  under  observation  who  were  treated  by 
Kuelz  seventeen  years  ago  and  more,  and  who  are 
still  in  excellent  health. 

In  the  meantime,  Kuelz's  original  method  has  re- 
quired much  modification  and  extension.  At  first  it 
was  thought  sufficient  to  determine  the  amount  of  car- 
bohydrate which  could  be  given  to  the  patient,  while 
ensuring  a  minimal  excretion  of  sugar  on  the  one 
hand  and  of  acetone  on  the  other.  This  is  a  rela- 
tively easy  problem  but  its  solution  does  not  satisfy 
us  at  the  present  time.  We  now  know  that  there  are 
no  diabetics  who  show  a  constant  degree  of  toler- 
ance for  carbohydrates.  It  varies  with  the  kind  of 
carbohydrate,  and  with  the  intervals  at  which  the 
carbohydrate  is  given.  Many  will  stand  the  same 
total  of  carbohydrate  much  better  when  the  whole 
amount  is  given  at  once;  others  must  be  given  small 
portions  frequently  during  the  day.  Many  stand  car- 
bohydrates best  in  the  morning,  others  in  the  after- 
noon or  evening.  Some  patients  show  a  much  higher 
degree  of  tolerance  when  they  take  muscular  exercise 
immediately  after  the  carbohydrate  food  (especially 
the  slight  cases) ;  others  have  to  rest  after  carbohy- 
drate food  (especially  the  severe  cases).  Many  pa- 
tients do  better  on  one  kind  of  carbohydrate  every 
day,  such  as  bread  alone  or  potato  alone,  or  fruit 
alone;  others  can  be  given  any  change  of  carbohydrate 
they  desire.  Often  it  makes  the  greatest  difference 
with  what  other  kind  of  food  the  carbohydrate  is 
mixed.     It  has  frequently  been  noted  that  it  is  here 


NEW  ASPECTS  OF  DIABETES  97 

especially  that  the  amount  and  kind  of  protein  is  im- 
portant. I  append  a  very  convincing  example  from 
a  man  aged  38. 

Day  Diet  Sugar  in  the  urine 

1  250  g.  Oatmeal,  300  g.  butter,  10  eggs  (=52 

g.  proteids)  o 

2  "  o 

3  "  o 

4  "  o 


s 

6 

7 
8 

250  g.  Oatmeal,  300  g.  butter,  250  g. 

(=52  g.  proteids) 
« 

beefsteak 

0 
■S-ig. 
12.3 
22.0 

9 

« 

274 

10 

green  vegetables,  eggs, 

butter 

5.0  day-time 
0     night-time 

250  g.  oatmeal,  300  g.  butter,  10  eggs  o 

12  "  o 

13  "  O 

Thus  we  cannot  simply  say  the  patient  tolerated  25 
grams  of  oatmeal,  but  we  must  add  that  this  amount 
was  only  borne  when  combined  with  eggs  and  not 
when  combined  with  meat. 

The  following  is  also  an  interesting  example:  A 
young  diabetic  girl  of  20,  who  had  a  short  time  be- 
fore had  slight  haematemesis,  for  two  weeks  took  2 
litres  of  milk  and  300  grams  of  cream,  and  10  lightly 
boiled  eggs   (52  grams  of  protein)   daily. 

Day  Diet  Sugar  in  the  urine 

1-14    2000  g.  milk,  300  g.   cream,   10  eggs    (=52 

gr.  proteids)  oto5gramm 


98         DISORDERS   OF   METABOLISM   AND   NUTRITION 


Day 

Diet 

Suga 

r  in  the  urine 

15 

2000  g.  milk, 

300  g. 

cream. 

ca. 

150  g. 

curds 

(=5^  gr.  casein) 

7.2  gr. 

16 

« 

12.8 

17 

« 

17.2 

18 

€( 

22.6 

19 

2000  g.  milk, 
proteids) 

300     g. 

cream', 

10 

eggs 

(=52 

14.8 

20 

« 

11.7 

21 

f( 

9-3 

22 

« 

8.1 

23-28  "  0-6  g. 

The  daily  excretion  of  sugar  in  the  urine  varied 
from  o  to  5  grams.  In  place  of  the  eggs  I  then  gave 
her  for  one  week  freshly  precipitated  washed  and 
pressed  casein,  which  she  took  mixed  with  cream. 
The  nitrogen  content  of  the  casein  was  determined 
daily,  and  the  patient  took  the  same  quantity  of  casein 
as  she  had  previously  taken  of  tgg  albumin.  I 
thought  that  the  patient  would  bear  casein  better  than 
eggs,  as  it  was  the  same  protein  as  that  which  she 
had  been  taking  in  considerable  quantities  in  her  milk, 
and  had  been  accustomed  to  take  well.  But  the  re- 
sult was  exactly  the  opposite;  increasing  amounts  of 
sugar  appeared  in  the  urine,  and  then  again  fell  to 
nothing,  or  a  mere  trace,  as  soon  as  she  returned  to 
the  diet  of  milk  and  eggs.  I  could  add  many  similar 
examples. 

Besides  the  influence  exerted  by  diet,  its  quantities 
and  the  way  in  which  it  is  mixed,  there  are  many 
other  factors  to  be  considered,  some  of  which  in- 
fluence the  glycosuria  and  the  acetonuria,  and  some  of 
which  are  of  importance  as  regards  the  general  health 


NEW  ASPECTS  OF  DIABETES  99 

of  the  patient.  Such,  for  instance,  is  the  amount 
which  the  patient  drinks,  the  influence  of  alcohol,  of 
baths  and  other  hydrotherapeutic  measures,  of  sleep, 
etc.  I  have  treated  this  subject  in  another  place 
("  Neurogenous  Diabetes,"  Medizin,  Klinik,  Heft  i, 
1 91 2),  and  have  shown  that  in  many  patients  the 
amount  of  glycosuria  is  increased  by  want  of  sleep, 
and  pointed  out  how  these  patients  may  be  improved 
by  treating  the  sleeplessness.  It  is  true  that  often  the 
matter  is  reversed;  in  many  patients  the  sleeplessness 
depends  on  the  diabetes,  that  is  on  the  injurious  in- 
fluence of  the  hyperglycsemia  on  the  nervous  system. 
The  best  and  most  reliable  method  of  improving  the 
sleep  is  then  an  energetic  regime.  These  are  the  com- 
monest cases.  The  others  in  which  sleeplessness  in- 
duces or  increases  glycosuria  are  much  more  rare.  In 
these  it  is  apparently  a  stimulation  of  the  sympathetic 
nervous  system  of  central  origin  which  is  communi- 
cated to  the  suprarenals.  There  are  then  mostly  other 
symptoms  of  sympathetic  stimulation.  The  cases  are 
usually  ones  with  slight  glycosuria,  and  marvelous  re- 
sults are  obtained  by  combining  the  diabetic  treat- 
ment with  bromides  or  codeine,  or  by  hydrotherapy 
or  residence  in  a  mountainous  country. 

You  will  see  therefore  that,  for  us,  every  case  of 
diabetes  bristles  with  questions;  we  need  all  our 
powers  of  observation  and  experience,  and  in  addi- 
tion to  chemical  investigations  and  a  measured  dietary 
we  need  also  a  minute  investigation  of  all  the  physical 
and  psychical  conditions  in  order  to  obtain  a  clear 


lOO      DISORDERS   OF   METABOLISM   AND   NUTRITION 

insight  into  the  case,  a  full  mead  of  success  for  the 
present  measures,  and  a  favorable  outlook  for  the 
future.  In  place  of  the  old-fashioned  single  test  of 
tolerance,  a  very  complicated  procedure  has  arisen, 
which  takes  into  consideration  the  extraordinary  varia- 
tions met  with  in  cases  of  diabetes ;  and  it  is  clear  that 
work  like  this  can  be  more  readily  carried  out  in  a 
suitable  nursing  home  than  by  observations  and  treat- 
ment undertaken  in  the  patient's  own  dwelling.  It  is 
not  my  intention  to  enter  in  detail  into  the  treatment 
of  diabetes,  but  there  are  some  important  questions 
which  must  not  be  left  aside. 

G.  Carbohydrates  or  Oatmeal  Cures 

You  all  know  that  twelve  years  agO'  I  made  the  dis- 
covery that  under  certain  circumstances  large  quanti- 
ties of  oatmeal  can  be  tolerated;  and  from  this  dis- 
covery the  so-called  "  oatmeal  cures  "  have  gradually 
been  evolved,  concerning  which  by  this  time  a  consider- 
able amount  of  literature  has  appeared.  For  the  first 
five  years  I  was  opposed  by  nearly  all  authors  who 
wrote  on  the  treatment  of  diabetes  with  oatmeal;  they 
had  not  sufificiently  observed  the  clear  directions  which 
I  had  given  for  carrying  out  the  oatmeal  cure,  and 
consequently  they  got  bad  results.  For  the  last  five 
years  things  have  been  different.  My  observations  have 
been  fully  confirmed  by  many  well-known  authors, 
and  I  now  have  to  complain  that  the  oatmeal  cure  has 
been  much  over-valued.  Partly  in  its  original  form 
and  partly  in  numerous  modifications  it  has  been  mucH 


NEW  ASPECTS  OF  DIABETES 


lOI 


more  frequently  and  exclusively  employed  than  is  ad- 
visable in  the  interest  of  diabetes.  I  have  myself 
from  time  to  time  warned  people  most  emphatically 
that  the  oatmeal  cure  was  not  to  be  regarded  as  a 
panacea  for  diabetes ;  this  warning  has  not  been  suffi- 
ciently taken  to  heart.  The  most  important  points  are 
illustrated  by  the  following  example,  taken  from  the 
case  of  a  fellow-countryman  of  your  own,  aged  48, 
whom  I  treated  some  time  ago  for  a  number  of  years. 


Day 

Diet 

Sugar 

Nitrogen 

NHs 

Aceton. 

I 

Restricted 

and  75  g-  bread 

70.8  g. 

18.2  g. 

2.2  g. 

2.6  g. 

2 

« 

« 

58.2 

195 

2.8 

2.7 

3 

« 

ft 

65.8 

207 

2.3 

2.5 

4 

<( 

;  no  carbohydrates 

43-3 

23.8 

3-2 

3-9 

5 

(( 

« 

34-7 

19-5 

2.1 

2.3 

6 

« 

<( 

352 

197 

2.0 

2.8 

7 

*( 

it 

337 

18.9 

2.2 

31 

8 

i( 

(( 

38.9 

20.1 

2.9 

3-8 

9 

t( 

and  25  g. 

oatmeal 

42.9 

176 

2.0 

1.8 

10 

(( 

** 

53.8 

18.9 

2.4 

17 

II 

« 

;  no  carbohydrates 

391 

20.6 

1.8 

2.2 

12 

« 

(( 

32.0 

17-5 

2.2 

27 

13 

ti 

« 

29.7 

195 

1.6 

2f.I 

14 

<{ 

u 

28.3 

18.6 

17 

1.6 

15 

Green  vegetables,  butter,  5 

eggs 

14. 1 

15.8 

1.2 

1.4 

16 

« 

it 

6.4 

9-9 

I.I 

1.2 

17 

<( 

H 

traces 

10.3 

1-5 

17 

18 

<( 

t( 

0 

11.8 

1-3 

1.2 

19 

250  gr. 
butter. 

oatmeal, 
100     g. 

300    g. 
glidin. 

(veget. 

prot.) 

0 

9.8 

0.9 

0.6 

20 

« 

u 

0 

12.1 

07 

0.3 

21 

<( 

u 

0 

8.8 

07 

0.1 

102      DISORDERS   OF    METABOLISM    AND   NUTRITION 

Day  Diet  Sugar    Nitrogen    NHs    Aceton. 


22 

Green 

vegetables,  butter  5 

eggs 

0 

7.9 

0.8 

0.25 

22> 

<( 

(( 

0 

8.3 

0.8 

0-3 

24 

Restricted ;  no  carbohydrates 

0 

13.7 

0.9 

0.2 

25 

« 

« 

0 

16. 1 

0.9 

0.15 

26 

it 

« 

0 

15.6 

I.I 

0.2 

27 

<( 

<( 

0 

18. 1 

1-3 

0.3 

28 

« 

and  25  g.  oatmeal 

0 

16.2 

0.9 

o.i 

29 

« 

« 

0 

15.4 

0.7 

0.2 

30 

« 

<< 

0 

17.2 

I.O 

0.35 

31 

(( 

« 

2.8 

16.7 

I.I 

0.4 

32 

(( 

;  no  carbohydrates 

0 

17.2 

1-3 

0.3 

33 

t( 

« 

0 

I6.I 

0.8 

0.2 

34 

« 

<( 

0 

19.3 

0.9 

0.15 

35 

« 

(( 

0 

16.4 

0.7 

0.08 

36 

a 

te 

0 

17.8 

0.9 

0.09 

Analysis  of  the  Table. — As  you  see,  the  case  was  one 
of  severe  diabetes  with  marked  acetonuria.  Carbohy- 
drates were  excluded  on  the  fourth  day,  but  the 
patient  did  not  cease  to  excrete  sugar.  The  glycosuria 
decreased  considerably,  and  finally  remained  at  about 
30  grams  per  day  (twelfth  to  fourteenth  day).  The 
ammonia  and  acetone  increased  in  the  beginning  which 
is  usual  when  bread  is  excluded,  but  the  gradual  spon- 
taneous fall  in  these  figures  gave  a  favorable  outlook 
for  the  future.  Then  on  the  9th  and  loth  days,  25 
grams  of  oatmeal  were  added,  with  very  bad  results, 
as  you  see.  I  then  cut  off  meat,  and  considerably 
diminished  the  total  amounts  of  protein,  as  can  be 
seen  from  the  figures  of  nitrogen  excretion.  By 
means  of  this  more  severe  regime,  I  succeeded  in 
diminishing  the  glycosuria  considerably,  and  on  the 
fourth    vegetable-day    it    had    entirely    disappeared. 


NEW   ASPECTS   OF   DIABETES  IO3 

Then  for  three  days  the  patient  was  subjected  to  a 
typical  oatmeal  diet,  with  the  addition  of  a  consider- 
able quantity  of  vegetable  protein.  We  gave  Klop- 
fer's  glidin,  as  it  is  far  the  best  among  the  vegetable 
protein-preparates.  No  sugar  was  excreted  and  the 
acetone  fell  enormously.  No  wonder  that  the  22nd 
and  23rd  day  (vegetable  diet)  produced  no  sugar. 
But  you  will  see  that  from  the  24th  day  onwards  the 
patient  was  able  to  bear  the  ordinary  diabetic  diet  rich 
in  proteids,  which  had  formerly  (days  8  to  11  and 
II  to  14)  resulted  in  the  output  of  large  quantities  of 
sugar.  Thus  in  the  interval  his  tolerance  had  been 
considerably  raised.  From  the  28th  to  the  31st  day 
I  interposed  an  experiment  with  25  grams  of  oatmeal 
(just  as  formerly  on  the  9th  and  loth  day).  The 
result  was  not  quite  satisfactory;  it  is  very  charac- 
teristic that  the  small  amount  of  25  grams  of  oat- 
meal was  not  well  borne  when  combined  with  meat 
diet,  whereas  formerly  ten  times  as  much  had  been 
exceedingly  well  tolerated. 

The  most  important  point  brought  out  by  this  table 
is,  that  a  system  of  diet  was  discovered  which  enabled 
a  large  amount  of  carbohydrate  to  be  absorbed  and 
assimilated  without  producing  glycosuria,  even  in  a 
severe  case  (days  19  to  21).  Although  we  must  not 
suppose  that  such  a  diet  could  be  carried  out  for  long, 
and  although  I  drew  attention  in  my  first  publications 
to  the  fact  that  a  long  continuance  of  such  a  regime 
destroys  its  efficacy,  yet  the  intermediate  result  is  of 
the  greatest  importance  for  the  whole  treatment  of 


I04      DISORDERS   OF   METABOLISM   AND   NUTRITION 

diabetes.  It  makes  all  the  difference  to  the  chemical 
processes  of  the  body,  that  we  can  now  employ  a 
method  by  means  of  which,  from  time  to  time,  we  can 
fight  the  harms  which  may  spring  from  long  periods 
of  restricted  diet.  You  will  see  from  the  table  the  re- 
markable effect  on  the  acetonuria  which  the  oatmeal 
can  produce.  The  acetone  at  once  fell,  and  thence- 
forth remained  at  a  low  level  not  only  for  a  few  days 
or  weeks,  but  as  I  must  say  for  many  years.  The 
immediate  and  permanent  results  are  not  always  so 
favorable  as  in  this  example;  but  cases  are  exceed- 
ingly numerous  in  which  the  oatmeal  cure  will  avert 
the  sudden  danger  of  severe  acidosis,  and  allow  us 
time  to  bring  the  sugar  production  gradually  into  cor- 
respondence with  the  sugar  consumption. 

In  order  to  obtain  a  good  result  from  the  oatmeal 
cure,  an  important  preliminary  is  to  reduce  the  gly- 
cosuria as  much  as  possible  by  previously  diminishing 
the  intake  of  food  to  a  marked  extent.  A  few 
vegetable  days  are  often  sufficient,  as  in  our  example; 
but  often  it  is  necessary  to  let  a  single  fast  day  pre- 
cede the  oatmeal  cure.  I  never  order  more  than  three 
oatmeal  days  in  succession;  on  the  other  hand,  it  is 
often  useful  to  let  a  vegetable  day  or  a  fast  day  fol- 
low immediately  on  the  oatmeal  days,  and  then  to  be- 
gin the  oatmeal  period  anew.  By  this  means,  the  ob- 
ject may  be  often  attained  which  the  first  oatmeal 
period  failed  to  accomplish. 

At  first  we  tried  to  explain  the  peculiar  action  of 
the  oatmeal  cures  by  the  special  properties  of  oatmeal 


NEW  ASPECTS  OF  DIABETES  IO5 

starch,  or  by  the  presence  of  special  chemical  sub- 
stances in  the  grain.  Further  researches,  undertaken 
by  myself  and  others,  have,  however,  shown  that  sim- 
ilar results  can  be  obtained  with  other  meals,  provided 
that  strict  adherence  is  given  to  the  rules  I  have  laid 
down,  that  is,  to  render  the  urine  free  from  sugar  be- 
forehand, and  so  give  no  meat  with  the  carbohydrates. 
I  have  myself  experimented  with  barley  meal,  banana 
meal,  linseed  meal,  peas  meal,  potatoes  and  apples; 
others  have  tried  wheat  meal  and  grape  sugar. 

These  new  experiences  by  widening  the  original  oat- 
meal cure,  no  doubt  mark  a  great  practical  and 
theoretical  advance  and  we  have  now  a  larger  choice, 
when  we  determine  to  institute  a  carbohydrate  cure. 
However,  it  has  become  increasingly  apparent  that 
it  was  a  peculiarly  lucky  chance  that  I  first  chose  oat- 
meal for  these  investigations;  for  the  different  kinds 
of  meal  have  not  by  any  means  the  same  value.  In 
most  cases  in  which  comparative  observations  were 
made,  oatmeal  showed  itself  to  be  much  the  best.  We 
do  not  yet  know  why  the  oatmeal  cure  sometimes  does 
good  and  sometimes  harm,  and  why  in  some  cases  one 
carbohydrate  and  in  others  another,  gives  better  re- 
sults. Much  work  is  yet  to  be  done  with  regard  to 
this,  which  will  no  doubt  yield  great  results  in  the 
treatment  of  severe  diabetes. 

Almost  all  the  authors  who  have  studied  the  effects 
of  large  quantities  of  oatmeal  and  other  carbohydrates 
on  diabetic  glycosuria,  agree  in  stating  that  only  tem- 
porary use  must  be  made  of  such  methods  of  cure. 


I06      DISORDERS   OF   METABOLISM   AND   NUTRITION 

They  should  be  inserted  between  periods  of  stricter 
diet,  especially  in  the  case  of  patients  who  can  only 
as  a  rule  be  allowed  very  small  quantities  of  carbohy- 
drate, if  any.  In  the  slighter  forms  where  from  80 
to  100  grams  of  bread  can  be  borne  without  glycosuria, 
such  cures  are  at  least  useless,  and  the  general  impres- 
sion is  that  they  do  more  harm  than  good.  Clearer 
indications  cannot  at  present  be  laid  down,  and  a  very 
considerable  amount  of  personal  experience  is  neces- 
sary before  one  can  predict  whether  this  method  of 
treatment  will  have  good  or  bad  results. 

There  is  also  another  form  of  "  carbohydrate  cure  " 
to  mention,  namely  that  proposed  by  R.  Kolisch  and 
G.  Rosenfeld,  and  other  workers.  They  base  their 
ideas  upon  the  type  of  nutrition  which  will  allow  the 
relatively  largest  amount  of  carbohydrates  to  be  used 
—  "  Greatest  oxidation  conditions  of  carbohydrates  '' 
as  Rosenfeld  calls  it  The  following  shows  an  ex- 
ample of  the  method : 


Sugar  as- 

Day 

Diet 

Sugar  in 

Sugar      similated 

Proteids 

Fat 

Carbohydr. 

the  urine 

average  (average) 

I 

II2g. 

160  g 

36  g. 

204  g. 

) 

2 

(( 

« 

(t 

18.2 

21.0    y  15.0 

3 

« 

« 

tt 

24.5 

) 

4 

" 

<i 

83  g. 

36.9 

5 

*t 

(» 

tt 

47.1 

) 

6 

ti 

u 

tt 

42.8 

47-S  >  35-5  g. 

7 

(t 

tt 

tt 

SI.3 

) 

8 

It 

*c 

tt 

594 

9 

81 

" 

(I 

56.2 

10 

« 

tt 

tt 

42.8 

■) 

II 

(( 

tt 

tt 

37.4 

39.8  y   43-2 

12 

(( 

tt 

tt 

32.9 

3 

13 

ii 

tt 

tt 

29.7 

NEW   ASPECTS   OF   DIABETES 


107 


Sugar  as- 
Day  Diet                        Sugar  in      Sugar      similated 
Proteids  Fat    Carbohydr.  the  urine    average  (average) 

14  81  160  g.        83  g.         35.2 

15  "  "               "           42.3 

16  "  "               "           41.8             43-5  y     39-5 

17  "  "               "           48.3 

18  "  "               "           49-8 


29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 

41 
42 

43 


19 

81 

" 

0 

20.2 

20 

« 

(( 

0 

8.2 

21 

« 

« 

0 

1.6 

22 

46 

« 

0 

0 

23-28 

81 

(( 

»( 

0 

112 

46 

81 


46 

81 

112 


20 


O 

o 
o 

30 


o 

30 


o 

0 
0 
0 

17  g 

0 
0 
0 
0 
0 
2.6 
0 
0 
0 

o 


This  is  an  instance  of  a  slight  case.  In  four  days 
after  the  considerable  quantity  of  83  grams  of  car- 
bohydrate was  withdrawn,  the  urine  became  sugar- 
free  (on  the  twenty-second  day)  and  it  remained  so 
on  carbohydrate- free  diet.  On  the  three  first  days,  out 
of  36  grams  of  carbohydrate  the  patient  assimilated 
15.0  grams  only;  when  the  intake  was  raised  to  83 
grams,  he  did  not  excrete  the  whole  difference  (47 
grams),  but  the  glycosuria  rose  from  16.5  grams  to 
47-5  grams,  and  the  assimilation  was  represented  by 


,I08      DISORDERS   OF   METABOLISM   AND   NUTRITION 

43.2  grams.  The  assimilation  improved  further, 
when  the  proteids  were  decreased,  but  the  betterment 
was  limited  practically  to  the  first  five  days  (9-13)  ; 
while  during  the  following  five  days  the  glycosuria 
rose  and  the  assimilation  was  less  complete.  In  the 
terminology  of  Rosenfeld  and  Kolisch  we  may  say: 
"  the  best  oxidation  conditions "  occurred  with  83 
grams  of  carbohydrate  and  a  simultaneous  strong  de- 
crease of  protein;  these  authors  would  consider 
rightly  that  this  is  the  ideal  dietary  for  this  case.  You 
will  at  once  see,  however,  that  there  are  two  chief 
drawbacks : 

(i)  The  assimilation  improves  at  the  commence- 
ment only;  later  it  decreases  as  the  tissues  come  under 
the  influence  of  the  continued  large  quantities  of  car- 
bohydrates. If  we  put  the  observation  in  the  form 
of  a  curve  we  shall  obtain  similar  curves  in  almost 
every  case;  and  I  am  of  the  opinion  that  the  authors, 
who  recommended  this  form  of  dieting,  did  not  con- 
tinue it  long  enough ;  otherwise  the  results  would  have 
been  less  favorable. 

(2)  By  this  method,  a  freedom  from  glycosuria  is 
never  attained.  I  need  only  refer  you  to  my  earlier 
statement  as  to  the  great  advantages  of  such  a  free- 
dom. 

The  second  part  of  the  table  (from  19  day  on- 
wards) shows  the  result  of  the  methods  I  employ,  and 
which  are  followed  by  nearly  all  recent  workers.  So 
soon  as  the  carbohydrate  was  entirely  withdrawn  the 
urine  became   free  from  sugar.     Then  we  added  a 


NEW  ASPECTS  OF  DIABETES  IO9 

small  quantity  of  carbohydrate  and  intercalated  from 
time  to  time  some  days  of  restricted  diet;  with  this, 
as  you  see,  the  general  result  was  much  more  encour- 
aging. On  the  31st  day,  we  were  able  to  obtain  the 
assimilation  of  as  much  carbohydrate  as  under  the 
"  best  oxidation  conditions  "  (14-18  day).  The  differ- 
ence was  only  9  grams  and  we  had  the  additional  ad- 
vantage, that  the  urine  remained  practically  free  from 
sugar.  The  result  would  have  been  more  favorable 
had  it  been  possible  to  keep  the  patient  longer  upon  a 
strict  diet.  However,  we  had  lost  so  much  time  dur- 
ing the  early  period  of  the  experiment  that  we  could 
only  allow  10  days  for  the  strict  diet. 

I  think,  speaking  generally,  that  this  method  of  the 
so-called  '*  best  oxidation  conditions  for  carbohy- 
drates "  is  not  to  be  recommended  in  cases,  in  which 
definite  decrease  of  carbohydrate  or  long  continued 
withdrawal  makes  the  urine  perfectly  sugar  free. 
The  method  certainly  provides  a  convenient  form  of 
treatment  for  these  patients;  but  its  advantages  re- 
late to  the  present  condition  only  —  it  does  not  pro- 
vide for  the  future.  I  regard  it  as  retrogressive  in 
character. 

It  is  another  matter  if  we  cannot  obtain  a  sugar 
free  urine  by  the  removal  of  carbohydrates  and  the 
danger  of  acidosis  threatens  in  the  distance.  For  such 
cases  the  method  is  not  new.  In  my  contribution  to 
the  "  Twentieth  Century  Practice  of  Medicine ''  made 
some  seventeen  years  ago,  you  will  find  that  I  sug- 
gested a  daily  intake  of  50-80  grams  of  carbohydrates 


no      DISORDERS   OF   METABOLISM   AND   NUTRITION 

for  such  cases,  proposing  also  that  short  periods  of 
restricted  diet  should  be  interposed.  This  is  the  stand- 
point of  the  majority  of  physicians  to-day. 

H.  Therapy  of  Acidosis  * 

I  must  not  close  this  section  on  the  dietetic  treat- 
ment of  diabetes  without  making  some  remarks  upon 
the  prophylaxis  and  treatment  of  acidosis.  I  shall  re- 
fer, however,  only  to  the  more  important  points.  I 
can  rely  upon  the  experience  gained  from  thousands 
of  cases  of  diabetes  which  I  have  treated  during  the 
last  years  in  hospitals  and  sanatoriums  for  weeks  and 
months,  and  have  daily  records  of  the  acetone  and 
oxy butyric  acid  outputs.  In  the  majority  of  these 
cases,  the  observations  have  been  repeated  and  con- 
trolled over  periods  of  many  years  = — some  of  them 
over  twenty  years. 

They  fall  into  two  main  groups : 

(i)  Those  cases  in  which  by  systematic  partial  or 
complete  restriction  of  carbohydrates  or  by  changes 
from  strict  to  liberal  diets,  a  sugar  free  or  almost 
sugar  free  urine  is  obtained.  Of  course,  one  of  the 
primary  objects  is  to  maintain  the  general  nutrition 
at  a  high  level;  this  is  naturally  the  first  care.  We 
find,  almost  without  exception,  that  the  acetonuria  is 
practically  undemonstrable,  or  that  it  sinks  to  a  danger 
free  level.  At  the  commencement,  while  the  patient 
is  getting  accustomed  to  the  dietary,  we  may  have  to 

*A  more  complete  description  of  the  treatment  in  acidosis  is 
to  be  found  in  the  last  chapter  of  this  book  —  page  126. 


NEW  ASPECTS  OF  DIABETES  III 

deal  with  an  increased  acetonuria;  the  ferric  chloride 
reaction  may  be  strongly  positive  and  oxybutyric  acid 
may  appear  in  the  urine.  This  is  the  reason  why  so 
many  physicians  consider  that  the  withdrawal  of  car- 
bohydrates is  dangerous;  they  relinquish  the  scheme 
of  restricted  diet  as  soon  as  these  phenomena  appear. 
I  believe  that,  if  they  have  not  a  wide  ex- 
perience, they  act  rightly  in  such  instances.  For  all 
problems  of  this  transitory  period  are  very  diffi- 
cult, and  only  an  extended  personal  experience  and 
the  most  careful  daily  control  and  daily  estimations  of 
acetone  enable  a  safe  steering  of  the  ship  past  these 
dangerous  rocks.  Everyone  meets  with  disastrous 
experiences  at  the  onset,  and  also  I  have  not  been  able 
to  escape  them.  In  the  first  time,  when  as  a  result 
of  closer  investigation  upon  diabetes,  partly  from 
theoretical  considerations  and  partly  because  of  the 
astonishingly  good  results  of  Kuelz  and  Stockvis,  I 
became  a  follower  of  the  restricted  diet  method.  I 
often  was  frightened  by  the  acetonuria  and  I  had  to 
ask  myself  if  this  was  really  the  best  way  after  all. 
The  time  required  to  accustom  a  patient,  without 
danger,  to  a  diet  which  ensures  sugar  free  urine,  varies 
considerably.  Sometimes  it  is  a  matter  of  days  only; 
sometimes  it  requires  weeks.  During  this  period  the 
tissues  learn  only  by  degrees  to  utilize  fatty  acids  with- 
out carbohydrates.  When  this  dangerous  transitory 
period  is  however  once  safely  passed,  there  follows  a 
long  interval  in  which,  in  spite  of  a  restricted  diet, 
acetonuria  need  not  be  feared.     We  have,  it  is  true. 


112      DISORDERS   OF    METABOLISM    AND   NUTRITION 

often  to  reckon  with  a  few  centigrammes,  or  even  i 
or  2  decigrammes,  of  acetone  in  the  total  daily  urine, 
because  we  cannot  make  the  chemical  changes  in  the 
fatty  acid  cleavage  entirely  independent  of  the  car- 
bohydrate intakes.  But  we  would  find  a  similar 
quantity  of  acetone  in  the  urines  of  healthy  individuals 
subjected  to  a  similar  dietary.  This  is  therefore  an 
alimentary  acetonuria  and  not  one  arising  from  the 
diabetes  and  leading  to  dangerous  results.  It  is  ad- 
visable that  this  slight  physiological  acetonuria  should 
be  tolerated  rather  than  an  attempt  made  to  overcome 
it  by  increasing  the  carbohydrate  intake  —  a  project 
which  in  the  end  would  most  certainly  make  the  dia- 
betic condition  worse.  Every  fear  that  the  small 
amount  of  acetonuria  could  increase  to  a  dangerous 
height  must  disappear  in  view  of  the  experience 
founded  on  fact.  Of  those  of  my  patients,  who  upon 
suitable  dietaries  permanently  kept  free  from  gly- 
cosuria, or  almost  so,  many  of  course  have  died.  I 
have  taken  the  trouble  to  ascertain  the  cause  of  death 
in  these  instances.  In  82  cases  there  was  not  a  single 
one  who  succumbed  to  diabetic  coma;  the  immediate 
causes  were  quite  otherwise :  —  pneumonia,  influenza, 
typhoid  fever,  tuberculosis,  cerebral  hemorrhage, 
arteriosclerosis,  carcinoma,  etc. 

Naturally,  we  cannot  obtain  the  best  results  in 
every  case;  many  continue  their  diabetic  career  un- 
checked, in  consequence  of  progressive  pancreatic  le- 
sions. Here  the  tolerance  gets  lower,  the  glycosuria 
cannot  be  stopped,  and  the  acetone  and  sugar  outputs 


NEW  ASPECTS  OF  DIABETES  113 

increase,  not  because  of  continued  restricted  diet,  but 
in  spite  of  these  wise  prescriptions. 

(2)  This  leads  us  on  to  other  cases  in  which  it  is 
impossible  to  render  the  urine  sugar  free  even  after 
restricted  diet.  To  obtain  sugar  free  urine  it  would 
be  necessary  to  apply  more  rigorous  regulations  and 
to  introduce  vegetable  and  oatcure  days.  As  I  have 
already  shown,  it  is  useful  to  interpose  such  days 
from  time  to  time,  so  as  to  lessen  the  excessive  rise 
in  the  sugar  output.  At  one  time,  when  the  oatcure 
and  its  counterfeits  were  not  known  and  when  for  these 
abstaining  periods  there  was  only  the  choice  between 
an  ordinary  restricted  and  a  vegetable  diet,  the  patient 
ran  each  time  a  fresh  danger  of  acidosis.  Now  that 
we  have  learned  to  combine  these  days  of  restricted 
diet  with  days  of  oatcure  etc.,  the  conditions  are  quite 
opposite.  We  gain  if  we  rightly  advance  facts  — • 
just  during  these  periods,  an  increased  tolerance  for 
carbohydrates  and  a  diminished  acetonuria.  Such 
vegetable  and  oatcure  periods  must  however  not  be 
used  too  freely  —  four  to  six  times  per  year  is  quite 
sufficient. 

In  the  long  intervening  periods  we  must  give  the 
patient  with  severe  glycosuria  a  relatively  large  amount 
of  carbohydrates.  He  will  naturally  excrete  much 
sugar,  but  it  makes  no  great  prognostic  difference, 
whether  the  output  reaches  40  or  60  grams  per  day  or 
more.  Single  vegetable  or  hunger  days  now  and  then 
must  curb  the  increasing  glycosuria.  We  must  pro- 
ceed in  this  way,  because  experience  has  shown  that 


114      DISORDERS   OF   METABOLISM    AND    NUTRITION 

by  these  means  the  acetonuria  is  kept  down  to  the  low- 
est level.  The  extent  of  acetonuria  varies  in  differ- 
ent cases,  and  it  is  common  knowledge  that  there  is 
in  severe  diabetes  a  tendency  to  a  gradual  augmenting 
of  the  acetone  excretion;  for  the  majority  of  cases  of 
diabetes  with  marked  glycosuria  tend  to  persistent 
progression.  These  are  the  cases  in  which,  according 
to  old  custom  and  the  newer  proposals  of  Rosenfeld 
and  Kolisch,  we  try  to  point  out  that  form  of  diet 
which  warrants  the  largest  quantity  of  carbohydrate 
to  be  assimilated,  whilst  we  lay  not  too  much  stress 
upon  the  amount  of  sugar  in  the  urine.  When  we 
endeavor  to  obtain  this  information,  we  find  that  it 
is  not  only  difHcult  but  requires  much  time,  as  each 
case  must  be  investigated  as  an  entity;  it  is  important 
to  follow  it  through  for  long  periods.  Hard  and  fast 
rules  do  more  harm  than  good. 

I  may  bring  forward  here  an  observation  made  in 
1902.  It  concerns  a  patient,  aged  52,  with  a  gly- 
cosuria of  ten  years  standing,  and  a  definite  acetonuria. 
However,  the  patient  was  able  to  work  for  another 
eight  years.     He  then  died  from  an  attack  of  apoplexy. 


Da: 

IT                              Diet 

Sugar 

Nitrogen 

Aceton 

I 

Restricted  diet  and  100 

g- 

bread 

80.2  g 

.     20.4  g. 

2.3  g. 

2 

K                                                        « 

92.3 

23.6 

2.8 

3 

U                                                        <( 

794 

22.8 

2.6 

4 

"               without 

bread 

62.8 

25-3 

3.6 

5 

M                                                         It 

58.1 

23.8 

3-9 

6 

tt                                                       it 

54-2 

24.1 

Z2 

7 

t*                                                       tt 

53-8 

19-3 

3.5 

8 

Vegetable-egg-day 

38.2 

14.8 

2.6 

9 

« 

21.1 

11.2 

1-9 

NEW  ASPECTS  OF  DIABETES         II5 

Day  Diet  Sugar  Nitrogen  Aceton 

10    Vegetable-egg-day  18.7  10.7  1.8 


II 

Oatmeal 

250 

gr.. 

butter 

300 

g. 

234 

6.8 

2.1 

12 

« 

u 

134 

5-9 

I.I 

13 

« 

it 

12.7 

8.1 

0.7 

14 

Vegetable 

:-eg8 

■-day 

2.8 

11.6 

0.8 

IS 

" 

0 

10.8 

1-3 

16 

(( 

0 

12.9 

1.6 

17 

Oatmeal 

250 

g.,  butter 

300 

g- 

0 

7-9 

0.7 

18 

<« 

t( 

0 

6.2 

0.3 

19 

(« 

(I 

0 

6.9 

0.4 

20 

Vegetable 

-egg 

-day 

0 

10.3 

0.8 

21 

(( 

0 

12.4 

0.9 

22  Vegetable-egg-day  and  200  g.  fish  6.9  14.2  0.8 

^3               "                                "  11.2  15.8  1.3 

24  Restricted  diet;  once  meat,  once  fish  20.4  18.2  1.9 

25  "                        "                  "  17-3  18.1  14 


26 

Restricted 

diet 

and  60 

g. 

bread 

29.1 

17.1 

I.I 

27 

« 

IC 

354 

16.8 

1-5 

28 

(( 

(t 

33-9 

18.2 

1.9 

29 

100 

g. 

bread 

49.9 

154 

1.3 

30 

((                           « 

55-0 

14.7 

0.8 

31 

«                           « 

62.7 

16.9 

06 

32f 

a                                      tt 

59-3 

15.3 

0.9 

Z3 

Vegetable-egg-day 

18.6 

10. 1 

09 

34 

Restricted  diet  and  120 

g- 

bread 

48.8 

147 

0.7 

35 

«                           « 

64.3 

15.2 

1-3 

36 

((                           (( 

78.6 

14.6 

1.6 

Z7 

«                           tt 

85.2 

16.7 

1.8 

38 

Vegetable-egg-day 

22.3 

11.7 

1-3 

39 

Restricted  diet  and  80 

g 

.  bread 

29.8 

16.8 

I.I 

40 

«                          It 

38.2 

18. 1 

0.8 

41 

ft                         tt 

40.1 

15.2 

0.7 

42 

tt                         tt 

35-3 

14.2 

0.5 

43 

tt                         tt 

34-9 

14.7 

0.6 

Il6      DISORDERS   OF    METABOLISM    AND   NUTRITION 

Day  Diet  Sugar  Nitrogen  Aceton 

44    Vegetable-egg-day  12.7  9.2         0.5 


45    Restricted   diet   without   bread 

16.9 

137 

0.6 

46 

20.3 

14.9 

0.9 

47 

20.7 

16. 1 

0.9 

48 

" 

"    and  80 

s- 

bread 

31.6 

154 

0.6 

49 

it 

«             (( 

34.2 

14.3 

0.7 

SO 

t( 

((                    a 

38.1 

14.9 

0.5 

SI 

t( 

(t                    (( 

36.7 

16.2 

0.6 

52 

(C 

it                    a 

35.8 

14.7 

0.5 

From  this  observation  we  learn  that  (i)  in  a  case 
of  severe  glycosuria,  by  a  simple  restriction  of  car- 
bohydrate it  w^as  not  possible  to  stop  the  glycosuria 
(days  4-10;  22-25;  44-47). 

(2)  The  marked  influence  of  the  interposed  vege- 
table and  oatcure  days  upon  the  raising  of  the  tolerance 
and  still  more  upon  the  diminution  of  the  acetonuria. 
The  good  effect  was  not  only  temporary;  it  persisted. 
Also  during  succeeding  months  and  years  the  acetone 
output  varied  from  0.5-1  gram.  These  are  not  dan- 
gerous quantities;  one  had  to  be  satisfied  with  them, 
for  except  in  the  times  when  the  oatcure  was  given 
we  could  not  obtain  any  lower  figures. 

(3)  80  grams  of  bread  as  an  addition  to  the  re- 
stricted diet  was  the  amount  which  was  best  borne. 
With  100-120  grams  of  bread  glycosuria  increased  too 
much  and  the  acetone  output  was  higher.  With  60 
grams  of  bread  glycosuria  appeared  nearly  to  an  equal 
extent  as  with  80  grams,  but  the  acetonuria  was  much 
more  marked. 

The  deductions  made  were  as  follows :  The  patient 
should  be  given  a  limited  amount  of  albumin  and  80 


NEW  ASPECTS  OF  DIABETES  II7 

grams  of  bread  daily;  every  fifth  day  a  vegetable-egg- 
day  should  be  ordered  and  every  second  month  a 
period  of  vegetable-oat  days  prescribed.  The  results 
justified  the  prescription;  for  many  years  the  patient 
exhibited  remarkable  energy  and  remained  free  from 
complications.  Of  course  it  was  necessary  to  repeat 
the  observations  from  time  to  time  in  order  to  see  if 
the  amount  of  bread  should  be  changed;  for  instance, 
I  found  that  in  the  following  year  the  lowest  acetone 
output  with  60  grams  of  bread;  this  indicated  improve- 
ment in  the  diabetic  process,  while  three  years  later 
it  was  preferable  to  raise  the  bread  to  lOO  grams,  be- 
cause this  was  the  quantity  which  produced  the  small- 
est excretion  of  acetone  bodies.  As  to  the  necessity 
of  prescribing  alkalies  to  all  patients  who  are  in  dan- 
ger of  acidosis  I  need  not  refer.  It  is  already  well 
known. 

I.  Drugs 

a.  Salicylates,  'Antipyrin,  Nervina,  etc, 

I  must  give  a  few  words  only  to  the  treatment  of 
diabetes  by  drugs.  We  know  of  certain  drugs  which 
tend  to  decrease  the  glycosuria,  namely  salicylates, 
antipyrin,  calomel,  jambul.  However,  we  must  bear 
in  mind  that  carefully  conducted  investigations  show 
that  the  powers  of  these  medicaments  are  somewhat 
limited.  The  positive  results  are  so  slight  that  we 
really  ought  to  consider  whether  we  are  right  in  sub- 
jecting the  patients  to  the  action  of  such  strong  drugs. 
Salicylic  acid  is  by  far  the  most  valuable.     At  one 


Il8      DISORDERS   OF    METABOLISM    AND   NUTRITION 

time  I  recommended  aspirin,  but  I  have  had  three  cases 
of  diabetes  lately  in  which  an  acute  nephritis  followed 
the  use  of  aspirin;  I  am  now  naturally  a  little  less  in- 
clined to  prescribe  it. 

Perhaps  the  most  useful  drug  is  nervina  and  among 
them  the  bromides,  veronal  and  opiates.  Of  the  last, 
I  prefer  the  new  Pantopon  to  the  older  and  much  used 
extractum  opii  and  codein.  If  we  reflect  as  to  the 
type  of  case  in  which  nervina  is  valuable,  we  are 
bound  to  conclude  that  the  benefit  is  much  more 
marked  in  nervous  patients,  particularly  those  suffering 
from  insomnia.  You  will  often  find  that  after  a  bad 
night,  the  glycosuria  is  more  obvious  than  after  a  good 
night.  I  can  bring  to  mind  cases  which  during  a  sleep- 
less period  and  a  restricted  diet  excreted  large  amounts 
of  sugar,  while  in  times  in  which  good  sleep  was  ob- 
tained by  the  use  of  veronal  or  bromides,  40  to  50 
grams  of  bread  could  be  taken  without  any  onset  of 
glycosuria  (see  Med.  Klinik,  No.  i,  1912.  "  Neuro- 
genous Diabetes'').  It  seems  most  probable  that  the 
nervina  lower  the  stimuli  which  are  sent  from  the  cen- 
tral nervous  system  to  the  liver  by  way  of  the  chromaf- 
fin system,  or  cut  them  out;  that  they  exert  an  in- 
fluence upon  the  internal  secretion  of  the  pancreas  is 
not  known  and  is  rather  improbable.  We  know,  how- 
ever, that  the  neurogenous  elements  in  glycosuria  vary 
considerably  in  different  individuals  and  so  it  is  easy 
to  understand  how  it  is  that  nervina  in  one  case  pro- 
duce good  results  while  in  others  they  are  unsatisfac- 
tory or  ineffective. 


NEW  ASPECTS  OF  DIABETES  II9 

Of  course  it  is  not  necessary  to  treat  all  the  nervous 
manifestations  of  diabetes  with  narcotics.  There  are 
other  methods,  such  as  hydrotherapy,  etc.  I  need  not 
go  into  this  aspect  of  the  question  just  now.  The  use 
of  narcotics  can  only  be  temporary;  in  the  end  they 
lead  to  more  disadvantages ;  that  goes  without  saying. 
If  we  ask  ourselves  whether  these  drugs  possess  the 
power  to  produce  a  marked  and  permanent  influence 
upon  the  metabolism  of  a  diabetic,  we  are  compelled 
to  give  regretfully  a  negative  reply.  They  are  only 
aids  with  a  limited  application. 

b.  Mineral  Waters 

What  I  have  said  about  drugs  must  also  be  stated 
about  mineral  waters  (Carlsbad,  Neuenahr,  Vichy, 
etc.).  No  one  believes  to-day  that  Carlsbad  and  the 
other  waters  possess  the  power  of  curing  diabetes. 
Yet  we  hear  about  satisfactory  results  from  this  cure. 
Its  value  lies  in  the  fact  that  at  least  for  a  month  the 
diabetic  at  Carlsbad  lives  carefully,  and  that  in  con- 
nection with  the  drinking  of  the  waters,  there  are  cer- 
tain dietary  restrictions  which  he  does  not  undergo 
in  his  own  house.  It  is  thus  quite  natural  for  the 
glycosuria  to  decrease  and  the  tolerance  to  rise;  in 
some  cases  the  improved  tolerance  may  last  for  some 
time,  although  the  advance  is  soon  lost  when  the  pa- 
tient returns  to  the  irregular  dietaries  of  home  life. 
In  addition,  in  the  health  resort  places  there  is  an  ab- 
sence of  unrest  and  worry  and  business  cares,  and  this 
tends  to  diminish  the  general  nervous  tension  and  to 


I20      DISORDERS   OF   METABOLISM    AND   NUTRITION 

weaken  the  harmful  nervous  stimuli.  In  slight  dia- 
betes there  is  also  the  regular  muscular  exercise  prac- 
ticed at  spas  which  in  itself  influences  the  glycosuria 
favorably.  In  other  patients,  there  are  the  complicat- 
mg  disturbances  of  the  stomach,  intestine,  liver  and 
kidney  which  lower  the  general  well  being  of  the  body, 
and  which  are  improved  by  a  "  drink-cure."  So  it  is 
that  the  majority  of  diabetics  look  back  upon  their 
"  drink-cure  ''  with  content  and  gratitude. 

These  drink-cures  at  Carlsbad,  Neuenahr,  etc.,  how- 
ever, are  only  of  real  use  for  the  future  if  the  patient, 
when  he  returns  home,  has  learned  to  order  his  life 
and  especially  his  nutrition  according  to  the  needs  of 
the  case.  But  in  the  spas  it  is  difficult  or  rather  im- 
possible to  attain  this  aim;  for  the  control  that  is  a 
necessary  basis  for  the  individual  dietetic  prescriptions, 
is  not  at  hand  in  the  spas.  This  can  be  done  much 
better  in  sanatoria  and  clinics.  By  these  remarks  I 
will  not  disparage  the  value  of  the  "  drink-cures." 
The  sanatorium  treatment  of  diabetes  is  a  neces- 
sary help  and  not  a  substitute  for  the  "  drink-cures." 
It  is  the  well  tried  basis  for  the  home-treatment. 
What  in  the  sanatorium  has  been  pointed  out 
as  the  best  form  of  his  diet,  that  the  patient  shall 
continue  at  home.  Remember,  not  the  one  month 
"  drink-cure  "  governs  his  future,  but  the  way  he  lives 
the  remaining  eleven  months  of  the  year,  decides  his 
life. 

If  on  the  other  side  the  therapeutic  extent  of  the 
mineral  water  cure  be  exaggerated,   it  constitutes  a 


NEW  ASPECTS  OF  DIABETES  121 

source  of  danger  for  the  diabetic,  who  is  liable  to 
imagine  that  he  has  done  all  that  is  necessary  for  his 
health  and  so  does  not  put  a  curb  on  his  diet  or  on 
his  general  condition  of  existence. 

c.  Specialties,  Secret  Medicines 

I  must  not  draw  to  a  close  without  considering  the 
mischief  caused  by  the  secret  remedies  and  patent 
medicines  which  are  constantly  being  advocated. 
Most  of  them  contain  much  stuff  that  is  quite  worth- 
less; they  also  contain  some  drugs  which  do  cause  a 
slight  diminution  in  the  glycosuria,  namely,  salicylic 
acid,  jambul  preparations  and  others.  In  others, 
arsenic  or  alkaloids  have  been  found;  these  are  drugs 
which  the  physician  prescribes  in  definite  doses  under 
a  guarantee  of  their  chemical  purity;  this  guarantee  is 
not  available  for  these  secret  remedies.  It  would  be 
interesting  to  follow  out  an  inquiry  into  the  why  and 
the  wherefore  of  the  demand  for  these  patent  remedies. 
The  manufacturer  and  retailer  insists,  either  in 
print  or  by  word  of  mouth,  that  during  the  course 
of  medicine  the  dietary  shall  be  free  from 
carbohydrates,  or  practically  so.  The  urinary  sugar 
then  of  course  sinks.  The  real  cause  is  the  well- 
recognized  dietary  limitations  and  the  restriction  of 
carbohydrates.  Later  the  carbohydrates  are  grad- 
ually increased  just  as  they  are  in  scientific  treatment, 
for  the  instructions  issued  from  the  manufacturer  of 
patent  medicines  and  specialties  are  copied  from 
medical  works. 


122      DISORDERS   OF    METABOLISM    AND    NUTRITION 

The  scientifically  trained  physician,  who  adds  cer- 
tain drugs  to  his  dietetic  treatment,  now  for  this  rea- 
son, now  for  that  one,  knows  that  the  drugs  play  only 
a  subordinate  part.  The  vendor  of  patent  medicines, 
on  the  other  hand,  labels  his  compound  as  the 
peculiarly  combative  and  specific  factor  in  the  treat- 
ment and  lays  claim  to  a  new  discovery  in  the  therapy 
of  the  disease.  We  must  not  go  so  far  as  to  say  that 
the  whole  matter  always  is  a  deliberate  fraud;  most 
frequently,  it  is  an  error  of  judgment  arising  from 
the  fact  that  the  vendors  of  these  specialties  have  not 
had  a  training  sufficiently  scientific  to  enable  them  to 
discriminate  between  cause  and  effect.^ 

1  As  an  example  of  these  defective  statements  I  may  mention 
L.  Bauer's  Antidiabeticum,  because  it  is  also  much  sold  widely 
in  this  country.  The  vendor  claims  that  this  preparation  exerts 
a  favorable  influence  upon  diabetes.  The  compound  is  a  mixture 
of  a  number  of  various  indifferent  extracts  and  contains,  in  ad- 
dition, some  salicylic  acid,  jambul  extract,  and  kola  extract. 
The  Deutsches  Kaiserliche  Gesundheitsamt,  that  is  the  Imperial 
German  office  for  public  health,  came  to  the  conclusion  that 
the  claim's  made  for  this  preparation  could  not  be  substantiated, 
and  that  the  favorable  results  depended  upon  the  observance  of 
the  directions  as  to  food.  Investigations  conducted  in  scientific 
institutions  have  confirmed  this  statement ;  in  view  of  the  continu- 
ally renewed  assertions  of  the  vendor,  the  "  Kaiserliche  Gesund- 
heitsamt "  again  carefully  went  into  the  matter,  and  once  more  is- 
sued its  destructive  verdict.  The  vendor  continued  to  make  anew 
certain  outrageous  claims  for  his  preparations,  so  Antidiabeticum 
was  placed  upon  the  black  list  of  patent  medicines  and  its  an- 
nouncements were  forbidden  in  Germany  under  a  penalty.  In 
spite  of  this  verdict  of  the  highest  recognized  authority  in  the 
empire,  the  vendor  would  not  acknowledge  his  error,  but 
elected  to  accuse  those  who  did  not  agree  with  him  of  a  grudge 
against  his  great  discovery.  The  cause  of  his  error  lies  near  to 
hand;  the  manufacturer  of  Antidiabeticum  is  a  layman  as  re- 


NEW  ASPECTS  OF  DIABETES  I23 

They  exhibit  unbounded  faith  in  their  statements, 
and  their  enthusiasm  converts  to  their  own  faulty 
standpoint,  not  only  the  laity  but  also  some  physicians. 
If  the  physician  falls  into  such  a  trap  it  is  always  be- 
cause he  does  not  understand  the  dietetic  treatment  of 
diabetes  or  has  not  taken  the  trouble  to  learn  it.  It 
often  happens  that  he  hears  of  one  of  his  patients  un- 
dergoing one  of  the  much  advertised  treatments;  the 
dietetic  instructions  sent  with  the  remedy  happen  to 
be  correct  ones,  and  the  doctor  is  astonished  at  the 
result.  A  deficiency  in  judgment  and  personal 
criticism  allows  the  doctor  to  assume  that  he  has  come 
across  something  which  is  unknown  in  medicial 
science. 

He  is  right  in  so  far  that  he  cannot  personally  ex- 
plain the  result,  but  he  occupies  a  false  position  when 
he  identifies  his  own  capabilities  with  that  of  the 
medical  scientist.  An  apology  for  his  standpoint  can 
only  be  based  upon  the  fact  that  the  therapy  of  dietetics 
in  general,  and  of  diabetes  in  particular,  demands  an 
acquaintance  with  a  large  mass  of  special  knowledge 
and  that  in  the  earlier  days  clinical  studies  in  this 
direction  were  very  limited,  while  even  now  in  many 
clinics  there  is  much  to  be  desired  in  this  regard. 
J.  Concluding  Remarks 

We  hope  that  this  will  undergo  a  change  for  the 

gards  scientific  and  medical  things.  It  is  easy  from  the  human 
standpoint  to  understand  that  he  has  committed  the  logical 
fault  of  considering  an  old  and  well  recognized  method  (re- 
strictions in  diet)  as  a  new  one,  after  having  colored  it  with  an 
insignificant  corollary   (the  drug). 


124      DISORDERS   OF    METABOLISM    AND    NUTRITION 

better  in  time.  Each  year  brings  further  knowledge 
and  shows  that  with  dietetic  therapy  successes  can  be 
obtained  which  are  unequaled  by  any  other  form  of 
treatment  in  the  diseases  of  internal  medicine.  We 
must  certainly  neither  forget  nor  neglect  to  give  an 
adequate  attention  to  the  wonderful  aids  yielded  by 
bacteriology,  serology  and  opotherapy;  all  these, 
methods,  however,  are  limited  in  their  applications; 
dietetics,  on  the  other  hand,  play  a  part  in  all  forms 
of  disease  and  extends  into  every  aspect  of  internal 
medicine.  Modern  dietetics  may  be  regarded  as  an 
offshoot  from  researches  upon  metabolism;  both  are 
intimately  connected.  I  am  proud  as  one  who  has 
made  many  contributions  on  this  subject,  to  realize 
that  dietetics  is  now  recognized  as  a  fruitful  branch 
of  scientific  medicine,  although  at  one  time  it  was  a 
little  known  and  neglected  step-child  which  the  practic- 
ing physician,  but  not  the  scientific  worker,  cared  for. 
The  cradle  of  scientific  dietetics  is  certainly  in  Ger- 
many, but  to-day  all  countries  are  taking  their  share 
in  the  work.  Most  valuable  are  the  stimuli  and  ad- 
vances which  this  country  has  contributed  to  the  study 
of  dietetics  as  a  science.  Your  Department  of  Agricul- 
ture and  your  physiologists,  Atwater,  Benedict,  Chit- 
tenden, Lusk,  Mendel  and  others,  working  upon  a 
broadly  conceived  and  bold  plan  of  action,  have  made 
fundamental  additions  to  the  laws  of  nutrition  which 
show  the  high  standard  of  knowledge  and  intense 
scientific  capacity  which,  to  its  imperishable  honor, 
modern  America  has  attained. 


NEW  ASPECTS  OF  DIABETES  1 25 

Every  subject  in  the  physiology  and  pathology  of 
metabolism  is  enriched  by  the  advances  made  in  the 
science  of  nutrition,  but  in  no  other  disease  have  the 
results  of  experimental  investigations  been  of  greater 
importance  than  that  upon  which  I  had  the  honor  to 
address  you,  namely  diabetes  mellitus. 


V:;l-itA'.i^'i^'i»Otai 


ACETONURIA:    ITS    INFLUENCE    ON    THE 
TREATMENT  OF  DIABETES  MELLITUS  * 

One  of  the  most  difficult  problems  in  the  treatment 
of  diabetes  is  how  to  regulate  the  diet  of  glycosurics 
who  are  excreting  acetone  bodies.  The  observation 
that  diabetic  coma  is  coincident  with  the  excretion  of 
large  quantities  of  acetone  bodies  has  led  us  to  consider 
the  acetone  bodies  as  the  most  dangerous  enemies  of  the 
diabetic,  and  no  doubt  rightly,  in  a  certain  sense. 
Thus,  both  in  practice  and  in  the  literature,  we  fre- 
quently find  it  stated  that  acetonuria  must  be  avoided 
under  all  circumstances,  and  that  it  is  better  to  suffer 
from  a  large  output  of  sugar  than  from  even  a  small 
output  of  acetone.  This  is  not  quite  a  correct  view, 
and  if  adhered  to  will  often  turn  the  treatment  of  dia- 
betes off  the  right  path.  The  risk  of  acetonuria  must 
certainly  not  be  underestimated,  neither  must  it  be  ex- 
aggerated. Diabetics  may  exhibit  an  acetonuria  of  a 
perfectly  harmless  nature,  which  must  be  regarded  as 
physiological. 

Before  describing  the  circumstances  and  direction  in 

which  the  occurrence  of  acetonuria  should  influence  the 

course  of  treatment  in  diabetes,  I  must  say  a  few  words 

on  the  origin  of  the  acetone  bodies.     This  will  make  it 

*This  lecture  was  read  before  the  St.  Louis  Medical  Society, 
September  30th,  1912.  It  goes  more  fully  into  the  very  impor- 
tant questions  on  acetonuria,  than  was  possible  in  the  previous 
lectures. 

126 


NEW    ASPECTS   OF  DIABETES  1 27 

easier  for  us  to  understand  what  follows.  We  have,  it 
is  true,  no  complete  knowledge  of  the  chemical  process 
which  gives  rise  to  the  production  of  acetone  bodies, 
nor  of  the  factors  which  control  this  process  quantita- 
tively; but  our  knowledge  is  sufficient  to  form  an  im- 
portant basis  in  practice. 

The  primary  acetone  bodies  are  B-oxybutyric  acid 
and  aceto-acetic  acid,  from  which  acetone  is  probably 
derived  as  a  secondary  product.  They  are  formed  in 
the  liver;  generally  speaking,  the  other  organs  take 
only  a  small  share  in  the  process.  By  far  the  most  im- 
portant sources  of  acetone  bodies  are  the  lower  fatty 
acids  in  which  the  carbon  atoms  are  arranged  in 
straight  chains,  and  certain  amido-fatty  acids.  This 
has  been  clearly  explained  by  G.  Embden's  researches. 
It  also  decides  the  old  question  as  to  whether  proteins 
share  in  the  formation  of  acetone  bodies.  This  is 
quite  possible,  as  the  amido-fatty  acids  are  components 
of  all  protein  molecules.  Both  theory  and  practical 
experience  show,  however,  that  only  small  amounts  are 
derived  from  this  source,  and  that  the  pure  fatty  acids 
are  by  far  the  most  important  bodies  in  this  connection. 

The  daily  metabolism  of  fatty  acids  is  enormous. 
We  must  recognize  the  possibility  (which  amounts  al- 
most to  a  probability)  that  the  acetone  bodies  are  nor- 
mal intermediate  products  in  the  decomposition  of  fatty 
acids.  How  then  does  it  come  about  that  no  acetone 
bodies,  or  only  traces  of  them,  appear  in  the  blood  and 
urine  under  normal  conditions  of  nutrition  and  metabo- 
lism ?    Although  suggested  by  a  few  earlier  researches, 


128      DISORDERS   OF   METABOLISM    AND   NUTRITION 

it  was  first  clearly  proved  by  the  remarkable  work  of 
F.  Hirschfeld  that  the  production  of  acetone  bodies  in 
larger  or  smaller  amounts  depends  entirely  on  the  non- 
co-operation  of  the  carbohydrates.  The  correctness  of 
this  view  can  be  easily  shown  by  suddenly  depriving  a 
healthy  person  of  carbohydrate  food.  One  of  my  for- 
mer assistants  carried  out  the  following  investigation 
upon  himself : 


Calories  of 

Oxybu- 

Day                              Diet 

the  food 

tyric-acid 

I               mixed 

2200 

0 

2    200  g.  meat,  200  g.  fat 

^130 

0.84  g. 

3    200g.      "      200  g.  " 

2130 

1.91 

4    250  g.      "      300  g.  " 

3228 

8.73 

5    250  g.      "      250  g.  " 

2658 

20.00 

6    250  g.      "      250  g.  "  , 

150  g. 

Reis 

3180 

2.21 

For  the  sake  of  clearness,  the  total  acetone  bodies 
are  reckoned  as  oxybutyric  acid.  You  see  that  acetone 
bodies  appear  at  once  when  the  carbohydrates  are  with- 
drawn from  the  diet,  and  that  they  continue  to  increase 
considerably  till  the  fourth  day,  when  they  again  imme- 
diately decrease  as  soon  as  150  grams  of  rice  are  added 
to  the  food.  This  is  an  alimentary  acetonuria;  it  is 
normal  and  physiological  in  origin. 

Relying  on  this  and  other  similar  examples,  the  fol- 
lowing statement  has  often  been  enunciated:  when  a 
sufficiently  large  amount  of  carbohydrate  is  burnt  up 
in  the  body,  the  fatty  acids  are  involved  in  the  process 
and  are  oxidized  to  carbon  dioxide  and  water.  G. 
Rosen f eld,  in  a  somewhat  different  connection,  coined 
the  expression  that  "  the  fats  are  burnt,  as  it  were,  in 


NEW  ASPECTS  OF  DIABETES  I29 

the  fire  of  the  carbohydrates."  But  when  no  carbohy- 
drates are  present,  the  decomposition  of  the  fatty  acids 
proceeds  differently;  by  oxidation  and  decomposition 
one  part  is  converted  into  acetone  bodies,  which  being 
difficult  to  oxidize,  pass  over  into  the  blood,  and  subse- 
quently into  the  urine  with  acids  substances  (oxy- 
butyric  acid  and  aceto-acetic  acid). 

The  quintessence  of  this  observation,  namely  the  fact 
that  the  normal  course  of  carbohydrate  metabolism  hin- 
ders acetonuria,  is  well  established ;  the  view,  however, 
that  the  principal  factor  is  the  oxidation  of  the  carbo- 
hydrates must  be  thrown  overboard,  especially  as  the 
liver  is  known  to  be  the  principal  seat  of  the  formation 
of  acetone  bodies.  The  amount  of  carbohydrate 
oxidized  in  the  liver  is  quite  insignificant  compared  to 
that  in  other  organs,  and  more  particularly  in  the 
muscles.  Moreover,  it  is  not  allowed  to  apply  to  dia- 
betes mellitus  (which  is  the  disease  always  quoted  as  an 
example)  ;  for  in  this  disease  the  oxidation  of  carbohy- 
drates is  not  at  all  diminished. 

We  are  drawn  more  and  more  to  the  conclusion  that 
it  is  the  special  carbohydrate  metabolism  in  the  liver 
which  in  some  way  prevents  acetonuria;  on  the  one 
hand  we  have  the  perpetual  formation  and  decompo- 
sition of  glycogen,  and  on  the  other,  its  presence  in  the 
liver  cells.  The  grape  sugar  in  the  blood  cannot  pre- 
vent the  formation  of  acetone  bodies ;  for  it  is  present 
under  the  conditions  which  are  specially  favorable  to 
their  formation.  In  diabetes  and  also  in  pyrexia,  the 
entire  blood  is  rich  in  sugar.     But  all  the  conditions  in 


130      DISORDERS   OF    METABOLISM    AND   NUTRITION 

which  we  meet  with  acetonuria  have  this  in  common, 
namely,  that  they  give  rise  to  a  diminution  in  the 
amount  of  glycogen;  and  if  we  take  into  consideration 
all  the  theoretical  conclusions  and  practical  observations 
we  can  now  quite  definitely  assert  that  it  is  the  presence 
of  glycogen  in  the  liver  cells  which  assures  the  normal 
decomposition  of  the  fatty  acids.  Deficiency  of  glyco- 
gen in  the  liver  cells,  on  the  contrary,  favors  the  forma- 
tion of  acetone  bodies.  We  do  not  know  whether  the 
glycogen  itself  is  utilized  in  the  normal  decomposition 
of  the  fatty  acids,  or  whether  it  is  at  times  combined 
with  the  fatty  acids  or  the  products  of  their  decompo- 
sition, or  whether  it  only  plays  the  part  of  a 
catalyzer. 

It  is  a  most  remarkable  fact  and  of  the  highest  im- 
portance in  the  treatment  of  diabetes  that  forms  of 
diet  which  at  first  lead  to  acetonuria,  after  a  time  cease 
to  do  so.  For  example,  acetonuria  is  markedly  de- 
creased after  extended  fasting  or  a  lengthy  diet  of 
protein  and  fat.  As  an  example,  I  will  quote  a  case  of 
fermentative  dyspepsia  in  which  I  ordered  a  diet  con- 
sisting solely  of  meat,  eggs,  bacon,  butter,  drained  sour 
milk  cheese,  and  various  kinds  of  over-ripe  cream 
cheese  during  a  period  of  three  weeks,  for  thera- 
peutic purposes.  This  was  practically  a  carbohydrate- 
free  diet.  The  daily  excretion  of  acetone  bodies  calcu- 
lated as  oxybutyric  acid  was : 

in    the    first    week average :  12.8  gramm 

"      "  second    "      "  8.3 

"      "    third      "     "  2.2 


NEW  ASPECTS  OF  DIABETES         I3I 

Judging  by  our  experience,  a  further  continuance  of 
the  same  diet  would  have  led  to  still  greater  reduction 
of  these  figures,  which  would  ultimately  have  reached 
zero. 

A  sort  of  tolerance,  therefore,  occurs,  probably  de- 
pending on  the  fact  that  the  liver  in  time  forms  glyco- 
gen (and  stores  it  up  in  large  quantities)  from  sub- 
stances which  it  does  not  use  for  this  purpose  under 
the  normal  conditions  of  nutrition.  For  instance,  it 
may  perhaps  use  the  amido  acids  of  the  proteins,  or 
the  fatty  acids  —  the  latter  in  the  same  way  in  which 
grape  sugar  is  formed  from  fatty  acids  and  afterwards 
decomposed  into  lactic  acid  in  the  blood  or  muscles. 
Lactic  acid,  however,  to  a  certain  extent,  inhibits  the 
formation  of  acetone. 

Nature  herself  shows  us  that  a  diet  of  protein  and  fat 
is  not  necessarily  followed  by  acetonuria.  The  inhab- 
itants of  the  Polar  regions  consume  very  little,  if  any, 
carbohydrate;  and  in  the  same  way,  carnivorous  ani- 
mals consume  none  at  all.  But  they  excrete  no  acetone 
bodies.  Thus  we  learn  that  omnivorous  man  can  con- 
tinue in  perfect  health  without  carbohydrates,  just  as 
can  a  carnivorous  animal. 

What  then  is  the  position  of  the  diabetic  with  regard 
to  this  matter  ?  The  diabetic  is  at  a  disadvantage  com- 
pared with  the  healthy  individual  as  regards  the  regu- 
lar decomposition  of  fatty  acids.  The  disturbance  of 
metabolism  which  he  suffers  consists  in  a  heightened 
tendency  to  sugar  formation  in  the  liver.  All  forms  of 
stimulation  which  act  on  the  liver  and  excite  it  to  sugar 


132      DISORDERS    OF    METABOLISM    AND    NUTRITION 

production,  result  in  the  formation  of  an  abnormally 
large  amount.  First  it  is  the  glycogen  which  falls  a 
victim  to  the  morbid  increase  in  sugar  formation.  The 
glycogen  disappears  from  the  cells  as  fast  as  it  is 
formed.  This,  at  any  rate,  is  what  happens  in  the  most 
severe  cases.  In  the  slighter  cases,  no  doubt,  a  certain 
amount  of  glycogen  can  be  retained  in  the  cells,  as  is 
shown  by  experiment  and  by  chemical  analysis  of  the 
liver  post-mortem.  Generally  speaking,  the  exagger- 
ated stimulus  to  sugar  formation  makes  the  retention 
of  glycogen  impossible,  and  thus  in  diabetics  the  bio- 
chemical essentials  for  acetonuria  are  produced.  We 
must  therefore  determine  the  significance  of  diabetic 
acetonuria,  both  as  regards  prognosis  and  treatment, 
from  this  point  of  view. 

The  course  of  an  acetonuria,  as  met  with  in  diabetics, 
varies  very  greatly.  On  theoretical  and  empirical 
grounds  we  must  distinguish  absolutely  between  the 
slight  and  severe  types  of  glycosuria;  and  also  in  these 
two  principal  groups  there  are  differences  which  are 
both  remarkable  in  themselves,  and  of  great  practical 
importance. 

A.  Slight  Glycosuria 

This  group  includes  those  cases  in  which  the  urine  is 
rendered  free  from  sugar  when  carbohydrates  are  much 
reduced,  or  entirely  excluded  from  the  diet.  Total  ex- 
clusion of  carbohydrates  is  only  practiced  at  the  begin- 
ning of  the  treatment;  after  a  short  time  small  quanti- 
ties are  again  introduced,  and  later  somewhat  larger 


NEW   ASPECTS   OF   DIABETES  1 33 

amounts;  due  caution  being  exercised  in  making  each 
increase.  On  practical  grounds  we  must  cease  to 
reckon  among  the  sHght  forms  those  cases  in  which 
the  urine  only  remains  free  from  sugar  when  all  carbo- 
hydrates are  excluded  for  a  lengthy  period. 

a.  Cases  in  which  Carbohydrates  had  been  Freely  Used 

Patients  who  have  hitherto  taken  a  mixed  diet  fairly 
rich  in  carbohydrates  are  discovered  to  have  sugar  in 
their  urine.  Three  or  four  per  cent.,  perhaps,  is 
found,  or  even  more.  Subsequent  search  for  acetone 
bodies  shows  that  they  are  absent. 

The  treatment  of  the  metabolic  disturbance  is  at 
once  taken  in  hand;  the  carbohydrates  are  decreased 
every  day,  till  after  about  a  week  they  are  completely 
excluded.  This  is  done  in  order  to  abolish  the  most 
powerful  of  all  the  factors  which  stimulate  the  manu- 
facture of  sugar  in  the  liver ;  and  to  spare  those  organs 
whose  functions  preside  over  sugar  formation  as  a 
whole;  and  by  this  means  to  give  them  time  and  op- 
portunity for  recovery.  This  protective  treatment,  or 
in  other  words,  the  period  of  strict  diet,  is  calculated 
to  last  for  about  two  or  three  weeks,  before  carbohy- 
drates are  again  very  cautiously  added  to  the  diet. 

The  sugar  in  the  urine  diminishes  and  reaches  zero 
after  a  few  days  of  strict  diet.  But  about  two  or 
three  days  after  we  have  excluded  the  carbohydrates, 
we  are  horrified  at  finding  a  strongly  positive  reaction 
with  chloride  of  iron;  a  quantitative  estimation  gives 
about  one  gram  of  acetone  and  2  to  5  grams  of  oxy- 


134      DISORDERS    OF    METABOLISM    AND   NUTRITION 

butyric  acid,  or  perhaps  considerably  more.  Unless 
the  rationale  of  the  formation  of  acetone  is  well  un- 
derstood, the  "  strict  diet "  will  usually  at  once  be 
abandoned.  The  doctor,  fearing  the  development  of 
coma,  will  order  carbohydrate  food  perhaps  in  lavish 
quantities  and  with  precipitant  haste.  But  he  is  wrong. 
By  this  he  throws  away  all  his  chances  of  practically 
influencing  the  morbid  processes  peculiar  to  diabetes. 
This  acetonuria  is  entirely  physiological;  healthy  in- 
dividuals would  have  behaved  in  exactly  the  same  man- 
ner, if  put  upon  the  same  diet.  It  is  an  alimentary, 
and  not  a  diabetic,  acetonuria.  I  refer  to  the  example 
given  above  —  namely  the  research  made  up  upon  him- 
self by  one  of  my  assistants.  If,  undeterred,  we  con- 
tinue the  strict  diet,  the  acetonuria  will  again  disappear 
in  about  eight  or  fourteen  days,  and  the  normal  for- 
mation of  acetone  will  again  be  established.  In  the 
many  thousand  cases  which  I  have  treated  in  the  course 
of  years,  I  have  never  seen  one  mishap  due  to  the  con- 
tinuance of  strict  diet  under  these  circumstances.  Ex- 
ample from  a  man  of  48  years  treated  in  1897 : 


Ferri-chlorid 

Day 

Diet 

Sugar 

Reaction  Aceton 

I     Mixed, 

rich  in  carbohydrates 

60.81 

?.           0 

0 

2 

« 

69.^ 

0 

0 

3     Severe 

and  100  g.  Bread 

52.4 

0 

0 

4 

«            (( 

48.3 

0 

0 

5 

so 

43-8 

0 

0.03 

6 

<(                      (( 

38.1 

0 

0.2 

7 

without  carbohydrates 

19.4 

0 

0.43 

8 

<(                  (( 

4-3 

+ 

07 

9 

«                  « 

0 

+ 

1-3 

10 

((                  « 

0 

++ 

1.8 

II         " 

11                          X 

0 

++ 

I.I 

NEW  ASPECTS  OF  DIABETES 


135 


Ferri-chlorid 

Day 

Diet 

Sugar  Reaction  Aceton 

12     Severe  without  carbohydrates 

0 

+ 

0.8 

13 

i            11 

0 

+ 

0.52 

14 

(           (t 

0 

traces 

0.43 

15 

I            t( 

0 

0 

0.32 

16 

(            <( 

0 

0 

0.33 

17 

(           (t 

0 

0 

0.19 

18 

(                       K 

0 

0 

0.07 

19 

(                       (I 

0 

0 

0.07 

2^0          * 

(                  te 

0 

0 

0.05 

21          * 

(                  (t                             « 

0 

0 

0.03 

22          * 

'      and  20  g.  Bread 

0 

0 

0.05 

23 

(               ((            (( 

0 

0 

0.03 

24 

*      no  carbohydrates 

0 

0 

0.02 

25 

'      and  30  g.  Bread 

0 

0 

0.02 

26 

'        ''     40 

0 

0 

0.02 

27 

*      no  carbohydrates 

0 

0 

traces 

28 

'      and  50  g.  Bread 

0 

0 

u 

29 

(               ((            <( 

0 

0 

(( 

30 

*      no  carbohydral 

.es 

0 

0 

(( 

I  have  chosen  this  instance  from  among  many  others, 
because  from  observations  on  this  case  during  a  period 
of  fifteen  years  I  know  that  acetone  bodies  have  never 
been  present  again  in  amounts  large  enough  for  quanti- 
tative estimation,  although  the  patient  restricts  him- 
self to  the  amount  of  only  50  to  80  grams  of 
bread,  and  frequently  for  a  time  observes  a  stricter 
diet.  A  higher  maximum  could  never  be  attained; 
as  soon  as  the  daily  intake  of  bread  or  its  equivalents 
reached  100  grams,  sugar  reappeared  in  a  few  days, 
if  not  immediately  —  a  sign  that  the  diabetic  tendency 
was  still  active.  The  general  condition  of  the  patient 
who  is  now  60  years  of  age  has  all  the  time  been  ex- 
cellent. 


136      DISORDERS   OF    METABOLISM    AND   NUTRITION 

h.  Cases  in  which  Carbohydrates  had  been  Disused 

Here  we  have  to  do  with  a  patient  who  has  known 
for  some  months  or  years  that  he  is  suffering  from 
diabetes,  and  throughout  this  period  has  confined  him- 
self to  a  diet  very  poor  in  carbohydrates.  However, 
he  has  taken  more  carbohydrate  than  he  could  tolerate, 
and  he  excretes  a  certain  amount  of  sugar  either  con- 
tinuously or  at  least  after  the  meals.  You  rightly  sup- 
pose that  a  rather  stricter  regulation  of  the  diet  is  all 
that  is  necessary  to  stop  the  glycosuria  altogether,  and 
you  consider  this  desirable  in  order  to  arrest  the  con- 
tinued hyperglycsemia  and  the  complications  which  it 
entails.  As  in  the  case  previously  described,  we  at  once 
enjoin  a  strict  diet,  and  test  continuously  for  ace- 
tonuria.  We  have  found  none  before  the  beginning 
of  the  treatment,  and  to  our  delight  we  see  that  it  does 
not  occur  during  the  period  of  strict  dieting.  The 
reaction  with  perchloride  of  iron  continues  nega- 
tive, and  the  qualitative  test  for  acetone  shows  at 
most  only  a  trace.  Why  is  this?  This  patient  was 
so  completely  accustomed  to  a  diet  poor  in  carbohy- 
drates, that  their  further  total  removal  does  not  ap- 
preciably disturb  the  carbohydrate  (that  is,  the  gly- 
cogen) economy  of  the  liver  cells.  Without  any  hesi- 
tation the  practitioner  will  carry  on  the  strict  diet  in 
these  cases  as  long  as  he  considers  it  advantageous  for 
these  or  any  other  reasons. 

When  you  have,  for  some  years,  placed  diabetics  on 
strict  dietetic  systems  again  and  again  —  which,   in 


NEW  ASPECTS  OF  DIABETES         137 

practice,  is  a  very  valuable  and  approved  procedure  — 
you  will  see  that  it  is  only  during  the  first  period  of 
severe  dieting,  which  the  patient  starts  after  a  mixed 
diet  rich  with  carbohydrates,  that  large  amounts  of 
acetone  are  found.  When,  in  the  intervals,  the 
patient  has  confined  himself  within  the  limit 
laid  down  for  him,  in  later  periods  of  strict  diet  there 
is  no  further  appearance  of  acetonuria  —  provided,  of 
course,  that  the  case  still  belongs  to  the  category  of 
slight  glycosurics. 


Year 

Diet 

Sugar 

Aceton 

1904 

(a)  mixed,      rich      in      carbo- 

40-50 gr.                    0 

hydrates 

(b)   14  days   severe  diet; 

0 

maxim:  1.4  gr. 

no  carbohydrates 

minim:  0.2   gr. 

(c)   II     months     severe     diet 

0 

traces. 

and  50-60  gr.  bread 

190S 

(a)  14  days  severe  diet; 

0 

traces ; 

no  carbohydrates 

maximum  0.05  gr. 

(b)   II  months  severe  diet  and 

70  gr.  bread 

0 

0  or  traces 

1906 

One  week  severe  diet;  no  car- 
bohydrates 

0 

0  or  traces 

To  curb  the  disease  for  length  of  time,  to  this  degree, 
it  is  not  always  possible;  for  many  cases,  originally 
slight,  carry  in  them  the  seeds  of  progressive  deteriora- 
tion, and  we  cannot  check  their  course  even  by  the  most 
careful  treatment,  although  we  may  be  able  to  prolong  it. 
From  what  I  have  already  said  concerning  acetonuria 
in  slight  cases  of  glycosuria  it  follows  that  it  requires 
no  special  attention  from  the  therapeutic  point  of  view. 
Of  course,  a  sharp  look-out  must  be  kept.     When  the 


,138      DISORDERS   OF   METABOLISM   AND   NUTRITION 

patient  is  under  careful  control  during  the  strict  diet- 
ing—  and  this  is  the  only  period  which  can  lead  to 
acetonuria  —  the  risks  are  so  small  that  for  a  long  time 
now  I  have  even  ceased  to  order  alkalies  when  patients 
suffering  from  obviously  slight  glycosuria  have  to  un- 
dergo periods  of  strict  diet. 

I  must  not  leave  this  subject  without  mentioning  that 
there  are  many  cases  of  obviously  slight  glycosuria  in 
which  a  few  decigrams  of  acetone  remain  in  the  urine 
and  the  reaction  with  perchloride  of  iron  never  entirely 
disappears ;  not  only  during  the  entire  period  of  strict 
dieting,  but  even  when  a  considerable  amount  of  bread 
is  added,  and  completely  assimilated  (about  60  to  70 
grams  of  bread  or  its  equivalent). 

Some  of  these  cases  are  harmless,  namely  those  in 
which  the  symptom  occurs  in  persons  of  late  middle 
age.  No  great  importance  need  be  attached  to  it, 
moreover,  when  it  is  observed  in  pregnant  women  with 
slight  diabetes.  Pregnancy  of  itself  predisposes  to 
acetonuria,  and  it  is  a  fact  well  established  by  expe- 
rience, that  at  other  times  also  the  amount  of  acetone 
bodies  formed  is  very  much  under  the  influence  of 
the  personal  equation.  Not  only  diabetics  but  also 
healthy  persons  show  great  variations  in  acetone  for- 
mation under  precisely  the  same  conditions  of  diet. 
In  healthy  persons,  kept  under  identical  experimental 
conditions,  the  acetone  values  may  show  a  difference 
of  300  to  400  per  cent.  When  a  man  with  a  family 
predisposition  towards  a  large  formation  of  acetone 
gets  diabetes,  acetone  values  may  easily  be  obtained 


NEW  ASPECTS  OF  DIABETES         1 39 

which  cause  anxiety  to  the  doctor;  and  it  often  re- 
quires a  long  and  detailed  study  before  one  can  be 
sure  that  it  is  a  case  of  harmless,  though  unusually 
large  physiological  acetone  formation,  and  not  a 
dangerous  pathological  condition.  The  distinction  is 
often  very  difficult  to  determine. 

Continued  acetone  excretion  of  about  one  decigram 
or  more  when  occurring  in  young  diabetics  must,  how- 
ever, be  regarded  with  the  greatest  mistrust  —  even  in 
obviously  slight  glycosuria.  In  this  stage  of  the  dis- 
ease, the  patients  will  tolerate  a  certain  amount  of  car- 
bohydrate, namely  about  80  to  100  grams,  provided 
that  it  is  distributed  in  small  portions  throughout  the 
day.  The  urine  will  then  remain  free  from  sugar, 
but  will  give  a  positive  acetone  reaction.  We  must 
take  this  as  a  sign  that  the  capacity  for  glycogen  stor- 
age in  the  liver  has  already  been  considerably  damaged. 
In  some  of  these  cases  I  have  estimated  the  sugar  in 
the  blood,  and  as  was  to  be  expected,  have  found  con- 
siderable hyperglycaemia.  With  our  present  knowl- 
edge we  cannot  be  surprised  that,  in  spite  of  this,  no 
sugar  appeared  in  the  urine ;  for  we  know  that  in  many 
diabetics  the  kidneys  become  very  impervious  to 
sugar,  even  in  the  absence  of  nephritis,  which  never  oc- 
curs early  in  such  cases.  The  prognosis  in  these  cases 
is  very  unfavorable.  I  have  never  seen  any  which 
did  not  assume  a  severe  form  in  a  year  or  two. 

In  spite  of  the  persistent  acetonuria,  I  would  recom- 
mend you  in  these  cases  to  stick  to  a  diet  which  allows 
no  sugar  to  pass  into  the  urine,  and  to  make  the  diet 


140      DISORDERS   OF   METABOLISM   AND   NUTRITION 

as  Strict  as  the  patient  can  bear.  It  is  the  only  method 
by  which  the  inevitable  turn  for  the  worse  can  pos- 
sibly be  postponed  for  long.  A  certain  amount  of 
alkalies  must  however  also  be  prescribed,  in  order  to 
ensure  the  removal  of  the  acid  products  of  metabolism. 
These,  moreover,  are  just  the  cases  which  are  specially 
suitable  for  the  occasional  application  of  an  oatmeal- 
cure. 

B.  Severe  Forms  of  Glycosuria 

The  matter  becomes  more  serious  when  we  have  to 
deal  with  the  cases  of  so-called  "  severe  glycosuria/* 
that  is,  those  cases  in  which  the  withdrawal  of  car- 
bohydrates alone  does  not  free  the  urine  from  sugar, 
and  in  which  to  accomplish  this  we  have  also  to  effect 
a  decrease  in  the  protein  constituents  of  the  diet.  If 
this  measure  is  successful  in  rendering  the  urine  free 
•from  sugar,  the  case  may  well  be  regarded  as  an  in- 
termediate form,  and  called  "  semi-severe.'*  Such 
cases  mostly  develop  from  cases  of  slight  glycosuria 
which  have  been  neglected,  and  their  place  in  the 
classification  is  entitled,  because  as  a  result  of  patient 
and  well-directed  treatment  they  can  be  brought  again 
to  their  original  slight  type.  In  the  genuinely  severe 
cases,  however,  it  is  only  very  exceptionally  that  we 
can  succeed  in  freeing  the  urine  from  sugar,  and  then 
only  for  a  short  time,  however  much  we  restrict  the 
protein  intake.  We  must  consider  separately  the  semi- 
severe  cases  in  which  some  improvement  is  possible, 
and  the  severe  ones;  for  with  regard  to  acetonuria 


NEW  ASPECTS  OF  DIABETES  I4I 

these  two  types  require  an  entirely  different  dietetic 
treatment. 

a.  Semi-Severe  Cases 

As  a  rule,  the  patient  has  been  a  diabetic  for  a  con- 
siderable time.  He  has  adopted  the  anti-diabetic  re- 
quirements which,  as  usually  ordered  by  medical  prac- 
titioners, contains  on  an  average  about  80  to  100 
grams  of  carbohydrate.  The  urine  contains  some  per- 
centage of  sugar,  but  gives  no  marked  reaction  with 
chloride  of  iron;  quantitative  estimations,  however, 
show  that  I  or  2  decigrams  of  acetone  can  be  obtained 
from  the  urine  during  twenty- four  hours.  The  gen- 
eral condition  is,  on  the  whole,  good,  and  the  nutrition 
quite  satisfactory.  Closer  investigation,  however, 
shows  that  in  most  cases  one  or  other  of  the  complica- 
tions of  diabetes  is  developing  or  already  present  — 
such  as  the  tendency  to  furunculosis,  disturbances  of 
vision,  neuralgic  or  neuritic  pains,  which  are  often  very 
incorrectly  diagnosed  as  "  gouty "  or  "  rheumatic,'* 
and  so  treated.  The  patient  has  often  been  sent  on 
previous  occasions  to  spas,  and  there  under  the  in- 
fluence of  a  stricter  regulation  of  diet  and  a  careful 
ordering  of  his  whole  manner  of  life,  has  ceased  to 
pass  sugar  and  remained  in  this  state  for  some  time. 
Later  on,  however,  these  "  cures  "  have  failed,  or  pro- 
duced only  a  quite  inappreciable  result. 

We  now  make  up  our  minds  to  try  to  convert  the 
semi-severe  type  of  glycosuria  to  the  slight  form  from 
which  it  originated.     It  is  not  anxiety  about  the  loss 


.142      DISORDERS   OF    METABOLISM    AND    NUTRITION 

of  sugar  which  makes  us  do  this,  but  the  danger  of 
prolonged  hyperglycaemia,  and  also  the  always  reap- 
pearing observation  that  it  is  just  these  cases  that  ex- 
hibit a  further  tendency  to  get  worse  when  once  they 
have  begun  to  be  progressive.  The  only  practicable 
method  is  the  dietetic;  at  times  this  not  only  involves 
very  severe  dietetic  measures,  but  at  the  same  time 
exposes  the  patient  to  the  risk  of  acetonuria.  It  is 
obvious  that  here  we  must  make  free  use  of  alkalies, 
but  a  mere  allusion  to  this  fact  is  all  that  is  necessary 
here;  I  shall  deal  with  the  therapeutic  use  of  alkalies 
in  detail  later  on. 

In  accordance  with  our  scheme  of  treatment  we 
slowly  reduce  the  input  of  carbohydrates  to  zero;  the 
glycosuria  diminishes,  but  does  not  disappear.  At  the 
same  time,  the  amount  of  acetone  bodies  in  the  urine 
rises  considerably;  the  reaction  with  chloride  of  iron 
becomes  strongly  positive,  and  we  find  i  to  2  grams  of 
acetone  in  twenty-four  hours'  urine.  Nevertheless  we 
persevere  with  the  restricted  diet,  and  the  amount  of 
acetone  continues  to  rise,  or  at  least  remains  very  high. 
No  doubt  by  this  we  are  exposing  the  patient  to  a  cer- 
tain amount  of  risk,  but  this  can  be  reduced  to  some 
extent  by  administering  about  lO  to  15  grams  of  bi- 
carbonate of  soda.  We  also  keep  a  sharp  lookout  on 
the  patient,  and  as  soon  as  we  discover  any  symptoms 
pointing  to  impending  diabetic  auto-intoxication  — 
such  as  headache,  excitement,  hyperaesthesia  of  the 
stomach,  etc. —  we  shall  add  carbohydrates  to  the  diet. 
We  have  been  advancing  too  rapidly,  and  must  wait 


NEW  ASPECTS  OF  DIABETES  I43 

a  little  while,  and  then  begin  again  to  try  and  eliminate 
the  carbohydrates. 

It  is  just  in  these  cases  that  we  get  brilliant  results 
by  interposing  from  time  to  time  periods  of  diet  com- 
posed exclusively  of  oatmeal  or  some  similar  food, 
accompanied  and  followed  by  two  or  three  days  of 
green  vegetable  food  and  eggs.  By  following  out  this 
dietetic  plan  quite  systematically  we  shall  find  that  in 
time  —  perhaps  after  three  or  four  weeks  or  longer  — 
the  glycosuria  will  diminish  and  ultimately  disappear. 
Although  the  patient  is  on  a  diet  absolutely  free  from 
carbohydrates,  except  on  the  days  when  he  takes  oat- 
meal, the  amount  of  acetone  bodies  in  the  urine  is 
diminished,  and  the  reaction  with  chloride  of  iron  dis- 
appears. Encouraged  by  this  pleasing  result,  we  leave 
the  patient  on  absolutely  strict  diet  not  only  for  a  few 
weeks,  but  during  many  months.  He  improves 
splendidly  and  puts  on  weight.  Later  on,  when  we 
add  some  carbohydrates  to  the  diet,  we  find  that  small 
quantities  can  now  be  borne  without  causing  sugar  to 
be  excreted.  We  have  achieved  our  aim  —  the  orig- 
inally obstinate  case  of  "  severe  glycosuria  "  has  been 
converted  into  a  "  slight  "  type. 

Example.  This  case  was  published  by  myself  some 
years  ago;  the  desired  result  was  attained  in  a  rela- 
tively short  time.  It  shows  at  the  same  time  both  the 
relative  and  absolute  advantages  of  the  oatmeal  cure.^ 

^The  first  part  of  this  table  is  published  in  von  Noorden, 
"Diabetes  Mellitus,  its  Pathological  Chemistry  and  Treatment," 
p.  191,  New  York,  E.  B.  Treat  &  Co.,  1905.  The  second  part  of 
the  table  has  not  been  published  before. 


144      DISORDERS   OF    METABOLISM    AND   NUTRITION 


Day 


Diet 


Ferri- 
Sugar  Aceton   chlorid-      NHs 
gramm  gramm  Reaction  gramm 


I 

Severe  +  lOO  g.  Bread 

89.2 

0.30 

0 

1.2 

2 

«         «           11 

84.9 

0.28 

0 

1-3 

3 

"       50 

78.3 

0.32 

0 

1.5 

4 

«                 ((                    n 

77.1 

0.58 

+ 

1.7 

5 

Severe  Diet 

50.4 

2.1 

++ 

3-2 

6 

"            u 

48.3 

2.4 

++ 

3.8 

7 

«            ^l 

58.9 

31 

++ 

4.3 

8 

Vegetable-egg-day 

28.2 

2.1 

++ 

2.9 

9 

"      " 

20.3 

1.9 

-H 

2.8 

10 

250  g.  oat,  300  g.  Butter 

38.3 

1.9 

++ 

2.4 

II 

<(            (<      «              << 

40.3 

1-3 

+ 

1.6 

12 

((            «      «              (( 

300 

0.9 

+ 

1.5 

13 

«            «      «              << 

20.1 

0.6 

+ 

I.I 

14 

Vegetable-egg-day 

8.0 

0.8 

+ 

1-3 

15 

((            «      <( 

2.3 

1.2 

+ 

1.8 

i6 

250  g.  oat,  300  g.  Butter 

18.3 

0.5 

0 

0.9 

17 

((                  ((          a                     (( 

5.6 

0.1 

0 

0.9 

i8 

ti                  <<          ((                     t< 

0 

0.05 

0 

I.O 

19 

Vegetable-egg-day 

0 

0.1 

0 

0.8 

20 

«            «      (( 

0 

0.1 

0 

0.8 

21 

Severe  Diet  with  meat 

0 

0.15 

0 

0.7 

22 

(C                      ((                  (I                  (( 

0 

0.18 

0 

1.0 

22, 

Severe  Diet  and  20  g.  Bread 

0 

0.12 

0 

0.9 

24 

((          <<      «     «              « 

0 

0.13 

0 

0.8 

25 

Severe  Diet ;  no  carbohydrates 

0 

0.14 

0 

0.9 

The  Severe  Diet  is  continued 

during  three  months. 

Then: 

I 

Severe  Diet 

0 

0.07 

0 

1.0 

2 

"+      "    and  20  g.  Bread 

0 

traces 

0 

0.9 

3 

"     "      40 

0 

« 

0 

I.I 

4 

"         "     "      50 

0 

(( 

0 

— 

5 

«         (t     ((      ^^           « 

traces 

(( 

0 

— 

6 

"         "     "    no  carbohydrates    0 

« 

0 

— 

NEW  ASPECTS  OF  DIABETES  I45 

The  next  table  shows  the  effect  of  a  long  continued 
restricted  diet. 


Day                             Food 

Sugar 

Aceton 

I     Severe +  75  gr.   Bread 

734  gr. 

2.0  gr. 

2     Fast-day 

day: 

9-8 

night : 

0 

0.4 

3     150  g.  Oats,  180  g.  Butter 

0.9 

15 

4    240  g.     "    300 

95 

1-5 

5     180  g.     "    200 

17 

I.O 

6    Vegetable-egg-day 

0.6 

0.6 

7     Severe  Diet;  no  carbohydrate 

10.2 

1.3 

0            «          ((        «            <( 

16.1 

2.2 

9            "          "        " 

20.9 

2.3 

10 

26.4 

1.8 

Now    followed    several    months    of 

severe 

diet   with 

a    daily 

maximum  of  20  g.  carbohydrates  after  a  year: 

1  Severe  +  35  g.  Bread  o  — 

2  "        45  "  o  — 

3  "        55  "  O  - 

4  "       65         "  traces  — 

I  beg  to  take  notice  of: 

1.  The  marked  decrease  in  the  output  of  the  sugar 
and  acetone  which  after  12  hours  had  fallen  from  73 
grams  to  9.8  grams,  and  at  the  end  of  twenty- four 
hours  to  practically  nil. 

2.  The  extraordinary  effect  of  the  three  days  "  oat- 
cure."  During  this  short  period  at  least  350  grams  of 
carbohydrate  were  assimilated. 

3.  The  unfavorable  influence  of  the  albumin-rich  but 
carbohydrate-free  diet  (7th  to  loth  day)  compared 
with  the  "oat-diet"  period  (3rd  to  5th  day). 
During  yonder  period  the  acetonuria  attained  a  great 
height. 


146      DISORDERS    OF    METABOLISM    AND   NUTRITION 

From  the  good  result  the  fast  days  and  especially 
the  oat  days  offered,  I  concluded  that  it  would  be  pos- 
sible to  reduce  this  case  to  a  slight  form  of  glycosuria. 
Thus  I  was  justified  in  prolonging  the  period  of  strict 
diet.  You  see  that  after  a  year,  the  tolerance  is  dis- 
tinctly increased  and  that  upon  a  diet  which  a  year 
previously  resulted  in  the  appearance  of  73  grams  of 
sugar  and  2  grams  of  acetone  there  is  now  only  a 
trace  of  sugar  and  acetone. 

What  has  taken  place  between  the  commencement 
and  the  close  of  the  treatment?  We  will  later  discuss 
the  reason  why  the  patient  had  only  slight  ketonuria 
in  the  beginning,  as  long  as  he  took  a  plenty  supply 
of  carbohydrates.  W^hen  all  carbohydrates  were  with- 
drawn, the  ketonuria  ought  to  have  increased 
since  the  diastatic  function  of  the  liver  was  being 
carried  on  at  an  enormous  height  and  the  small 
amount  of  glycogen  formed  from  albumins  was 
rapidly  carried  off  from  the  cells.  Without  the  in- 
fluence of  the  glycogen,  the  cleavage  of  fatty 
acids  followed  the  wrong  course.  In  the  meantime, 
however,  we  have  methodically  and  intentionally 
spared  the  glycogenic  functions  of  the  liver  and  this 
calming  treatment  (Schonungs  therapie)  has  resulted 
in  a  decrease  of  the  irritant  of  the  sugar  forming  func- 
tion. The  cells  have  in  part  regained  their  activities 
to  utilize  glycogen  and  at  this  moment  the  acetone 
bodies  begin  to  decrease.  We  benefited  the  patient 
a  great  deal.     His  general  condition  improved,  the 


NEW  ASPECTS  OF  DIABETES  I47 

tendency  to  ketonuria  has  disappeared  and  the  sugar 
production  returned  to  its  normal  level  —  a  level,  how- 
ever, which  is  maintained  only  so  long  as  the  sugar 
manufacturing  is  not  too  much  overburdened.  If  we 
were  to  give  carbohydrates  again  either  in  too  great  an 
amount  or  too  rapidly,  then  the  old  conditions  at  once 
would  return. 

What  would  have  happened  if  we  had  been 
frightened  by  the  intense  acetonuria  and  had  returned 
at  once  to  the  original  quantity  of  carbohydrate  or 
even  increased  it?  The  ketonuria  would  also  have 
disappeared  —  perhaps  not  forever,  but  still  for  a 
length  of  time.  This  is  remarkable,  and  is  not  easily 
explained  by  certain  theories  of  ketonuria.  It  is  not 
difficult  to  show  that  the  ketonuria  disappears,  al- 
though the  consumed  carbohydrates  are  not  at  all  util- 
ized, namely,  although  the  quantity  of  sugar  in  the  urine 
exceeds  that  of  the  total  carbohydrates  of  the  food. 

I  may  mention  a  case  which  occurred  when  I  was 
still  an  assistant  in  Gerhardt's  Clinic.  I  was  then  of 
the  opinion  that  in  every  case  of  acetonuria  —  even 
when  of  transitory  form  only  —  a  restricted  diet  were 
not  admissible. 

In  the  following  table  the  carbohydrates  present  in 
the  restricted  diet  are  calculated  as  20  grams.  In 
this  the  preformed  carbohydrate  groups  of  the  pro- 
teins are  included.  The  assumed  amount  of  20  grams 
is  rather  too  high  than  too  low,  as  the  food  was  very 
carefully  selected. 


148      DISORDERS   OF    METABOLISM    AND   NUTRITION 


Carbohydrate    Differ- 

Day                  Food 

Acetone  in  food    in  urine    ence 

I     Severe  +  100  g.  Bread 

0.1 1  g.       80  g.      72.8  g.      +7.2  g. 

2 

0.18           80          79.3          +0.7 

3 

0.^3          80          71.4         +8.6 

4         « 

0.22          80         80.6         -0.6 

5 

Severe  without  additions 

0.61 

20 

59.3 

-39-3 

6 

»            «                (( 

1.7 

20 

59.2 

-30.2 

7 

<{            t<               (( 

^.l 

20 

54.3 

-34.3 

8  Severe  + 120  g.  Bread  1.9  92  66.3  +25.7 

9  "  "  "  1.4  92  784  +136 

10  "  "  "  0.8  92  82.5  +  9.5 

11  "  "  "  0.4  92  90.1  +  0.9 

12  "  "  "  0.2  92  99.3  -  T.z 

13  "  "  "  0.3  92  92.8  -  0.8 

14  "  "  "  0.18  92  102.6  -10.6 


We  see  that  the  large  amount  of  120  grams  of  bread 
is  associated  with  a  decrease  of  the  acetonuria  and  we 
see  its  return  to  the  quantity  present  at  the  beginning 
of  the  experiment,  although  the  tolerance  for  carbohy- 
drates is  altered  for  the  worse.  Just  when  not  the 
smallest  amount  of  the  consumed  carbohydrates  was 
assimilated,  we  met  with  the  lowest  output  of  acetone. 

In  such  instances  it  is  only  possible  to  explain  the 
decreased  acetonuria  by  assuming  that  the  carbohy- 
drate streaming  in  from  the  intestine  to  the  liver, 
even  in  severe  diabetes,  does  not  simply  pass 
through  the  liver,  but  is  taken  up  by  the  cells  and  re- 
mains there  as  glycogen  for  a  short  time  before  it  falls 
a  victim  to  the  increasing  wave  of  diastatic  action. 
When  it  happens  that  the  period  of  retention  is  not  too 
short,  the  contact  action  of  the  glycogen  upon  the  fatty 


NEW  ASPECTS  OF  DIABETES  I49 

acids  suffices  for  their  return  to  their  normal  course 
of  cleavage. 

We  thus  see  that  the  ketonuria  may  yield  both  to 
carbohydrate  starvation  and  carbohydrate  abundance. 
The  practitioner  may  perhaps  regard  the  latter  way  as 
the  least  dangerous,  but  this  is  not  so.  Although  for 
the  moment  it  may  be  easier,  it  is  not  con- 
sonant with  the  duty  of  the  physician  in  his  care  for 
the  future.  Such  an  apparently  agreeable  allowance 
of  carbohydrate  leads  with  unfailing  regularity  to  a 
disorder  of  the  sugar  factory  and  increases  the  tend- 
ency to  unbridled  production  of  sugar  —  in  one  case 
slowly  and  another  rapidly  —  and  exposes  the  patient 
to  all  the  dangers  associated  with  permanent  hyper- 
glycsemia  —  dangers  which  we  fear  as  the  complica- 
tions of  diabetes.  It  is  certainly  true  that  it  is  not 
every  diabetic  who  shows  this  tendency  to  get  worse. 
Many  cases  remain  in  the  same  condition  for  years, 
or  decades,  or  even  improve  in  spite  of  neglect  from 
the  dietetic  standpoint;  but  in  the  transitional  type  of 
case  —  between  the  sHght  and  severe  glycosurias  — 
which  we  are  now  discussing,  it  is  the  rule  that  every 
lack  of  dietetic  observance  means  a  step  backwards  for 
the  patient. 

In  cases  therefore  in  which  there  is  the  possibility 
of  return  of  slight  glycosuria,  I  hold  that  it  is  not  per- 
missible to  make  such  a  draft  upon  the  future  for  the 
sake  of  the  momentary  comfort.  I  must  advance  the 
view  that  in  every  case  of  severe  or  medium  glycosuria 
the  hyperglycsemia  and  glycosuria  must  be  reduced  to 


150      DISORDERS   OF   METABOLISM   AND   NUTRITION 

the  smallest  possible  amount,  in  spite  of  an  unavoidable 
period  of  increased  and  perhaps  dangerous  acetone  for- 
mation, and  that  the  tendency  to  ketonuria  must  be 
treated  not  through  the  allowance  of  carbohydrate  but 
by  a  systematic  calming  of  the  sugar  forming  processes. 
I  am  not  alone  in  this  view.  Minkowski,  Naunyn  and 
Luethje  are  of  the  same  opinion,  and  Luethje  (Thera- 
peut.  Monatshefte,  1910,  No.  8)  has  recently  published 
a  remarkable  paper  upon  the  dietetic  treatment  in 
which  he  comes  to  the  same  conclusions.  I  may  also 
add  that  my  experience  goes  to  show  that  the  diabetics 
who  have  been  most  benefited  by  my  treatment  are 
those  in  which  a  severe  glycosuria  resulting  from  neg- 
lected dieting  has  been  curbed  by  a  long  period  of 
strict  carbohydrate  free  food. 

h.  The  Redly  Severe  Forms  of  Glycosuria 

There  are  cases,  however,  which  cannot  be  brought 
within  these  limits.  In  spite  of  all  the  dodges  and 
tricks  of  an  extended  experience,  the  ketonuria  pro- 
gresses to  an  intolerable  height,  so  soon  as  we  cut  off  or 
only  decrease  the  carbohydrate  and  it  remains  at  this 
height  so  long  as  we  continue  this  regime.  We  have 
to  expect  in  these  cases  that  even  a  carbohydrate  rich 
diet  will  not  lead  to  a  disappearance  of  the  ketonuria; 
it  only  moderates  the  output.  These  are  the  worst 
type  of  cases  —  the  end  stage  of  severe  glycosuria  — 
which  for  months  or  years,  however,  are  compatible 
with  the  continuation  of  life.     As  a  rule  they  tend  to 


NEW  ASPECTS  OF  DIABETES         I5I 

one  end  and  are  regarded  as  hopeless.  One  must  not, 
however,  lay  down  one's  arms  straight  away;  a  num- 
ber of  them  yield  to  patience  and  resourcefulness  and 
return  to  a  milder  type.  It  is  not  easy  to  say  when 
this  will  occur  and  why  it  is.  In  some  cases  of  severe 
diabetes,  spontaneous  improvement  now  and  then  sets 
in;  on  the  other  side  there  are  many  cases  of  slight 
diabetes  in  which  dangerous  symptoms  temporarily 
appear,  so  that  we  fear  we  must  give  up  hope.  We 
see  this  specially  in  acute  infections,  among  which 
staphylococcal,  streptococcal,  and  influenza  are  the 
most  important.  I  remember  several  cases  of  furun- 
culosis  and  staphylococcal  sepsis,  in  which  within  a 
week  a  slight  diabetes  progressed  to  a  severe  glycosuria 
with  marked  acetonuria.  When  the  infection  ter- 
minated the  diabetes  assumed  again  the  milder  form. 

There  remain,  however,  as  we  have  indicated,  cer- 
tain cases  of  severe  diabetes  which  do  not  return  to 
the  slighter  types.  We  meet  with  them  at  all  ages,  but 
most  frequently  in  children  and  young  adults.  On  a 
liberal  diet  the  ketonuria  is  ameliorated;  on  a  re- 
stricted diet  it  progresses  continuously.  Here  the  re- 
striction of  carbohydrates  is  not  allowed.  We  then 
must  remember  that  the  intestinal  carbohydrates 
streaming  to  the  liver,  to  some  extent  control  the 
amount  of  ketonaemia ;  and  we  must  concern  ourselves 
with  the  immediate  dangers  of  the  condition  without 
giving  too  much  thought  to  the  future. 

According  to  our  hypothesis,  in  such  cases  the  car- 
bohydrate of  the  food  entering  the  liver  by  the  portal 


152      DISORDERS   OF   METABOLISM    AND   NUTRITION 

vein  remains  in  the  hepatic  cells  for  a  short  time  as 
glycogen  and  so  exerts  a  very  slight  but  necessary 
influence  on  the  cleavage  of  the  fatty  acids;  the  gly- 
cogen formation,  however,  is  far  too  small  to  inhibit 
completely  the  abnormal  cleavage  of  fatty  acids.  In 
these  cases  we  have  to  content  ourselves  to  curb  the 
excess  of  the  sugar  output  by  prescribing  three  or  four 
fast  days  each  month.  Experience  shows  that  the 
withdrawal  of  carbohydrates  in  this  manner  does  not 
cause  an  increased  ketonuria;  there  is  rather  a  lower- 
ing of  the  output,  just  contrary  as  we  find  in  the 
healthy  when  starvation  or  carbohydrate  restriction  is 
practiced.  I  formerly  ordered  that  every  eighth  or 
tenth  day  shall  be  a  vegetable-egg- fat-day.  I  even 
now  go  further  and,  following  Naunyn,  advise  a  hun- 
ger day,  when  only  tea,  weak  bouillon  and  large 
amounts  of  brandy  and  soda  are  permitted;  the  patient 
on  this  day  remains  in  bed  so  that  the  sugar  forming 
organs  may  be  spared  to  the  utmost.  As  a  result  the 
urine  often  becomes  sugar  free  and  the  ketonuria 
shows  a  distinct  decrease,  even  in  the  most  severe 
cases.  We  need  have  no  fears  that  the  hunger  day 
will  damage  seriously  the  general  nutrition.  Of 
course  the  body  weight  falls  on  the  fast  day,  but  the 
loss  is  rapidly  made  up  and  by  this  combined  method, 
which  the  table  demonstrates  we  often  obtain  consider- 
able increases  in  weight. 

Sugar  Aceton 

Day  Food  in  the  urine  NHs      in  the  urine 

1-7      Mixed,  with  100  gr.  carbo- 
hydrates 80-110  gr.     2-3   gr.      2.1-3.0  gr. 


NEW  ASPECTS  OF  DIABETES  1 53 


Sugar  Aceton 

Day  Food  in  the  urine  NH3         in  the  urine 

8      hunger-bed-day  day:  10.5      "|  "| 

night:  trace.  J  j 

9-16    Mixed,  with  100  gr.  carbo-  60-85  2.0-2.5  1.8-2.8 

hydrates 


0.8 


17    hunger-bed-day  day:    8.4    "1  "1 

night:       o   J         ^'^  } 


0.9 


In  the  more  advanced  stages  of  the  diabetic  process 
the  diastatic  action  is  so  disturbed  that  the  formation 
of  glycogen  is  without  any  beneficial  effect.  The  ex- 
tent of  the  ketonuria  remains  almost  unaffected  by 
the  administration  or  withdrawal  of  carbohydrates. 
Hence  one  does  not  select  to  cause  the  patient  unneces- 
sary and  useless  restriction.  This  stage  is  rarely  as- 
sociated with  a  return  to  milder  forms;  it  progresses 
unhindered  towards  coma. 

I  have  only  indicated  the  more  important  types  of 
ketonuria  and  mentioned  examples  which  best  illus- 
trate them.  There  are,  of  course,  transitional  and  in- 
termediate classes,  but  these  are  easy  to  orientiate,  once 
one  is  able  to  define  the  chief  forms  of  the  condition. 

C.  Special  Indications 

We  may  now  consider  the  use  and  importance  of 
certain  therapeutic  measures  in  the  prevention  and  the 
treatment  of  acetonaemia. 

a.  Alkaline  Therapy 

This  IS  based  chiefly  on  the  views  of  the  school  of 
Schmiedeberg  and  Naunyn  that  in  the  diabetic  auto- 
intoxication abnormal  acids  appear  in  the  blood  stream. 


I'54      DISORDERS    OF    METABOLISM    AND   NUTRITION 

Whether  or  not  the  matter  is  one  of  poisoning  by  acids, 
namely  the  action  of  acid  ions  upon  tissues  and  of  loss 
of  the  fixed  alkalies  required  for  the  neutralization  of 
the  acids,  is  still  an  unsettled  question.  Such  views 
appear  to  me  not  quite  right,  for  there  is  most  prob- 
ably a  specific  toxic  action  of  certain  acids,  which  in- 
crease the  acid  influence  of  the  aceto-acetic  and  oxy- 
butyric  acids.  We  must  not,  however,  dip  further 
into  this  interesting  theoretical  question  just  now.  At 
all  events,  we  hold  that  when  large  quantities  of  acids 
appear  in  the  tissues,  we  must  administer  a  full  mead 
of  alkalies.  It  is  a  widely  spread  though  false  view 
that  alkalies  diminish  or  hinder  the  formation  of  ace- 
tone bodies.  In  this  regard  their  influence  is  of  the 
slightest.  The  favorable  results  are  due  to  the  fact 
that  the  alkalies  combine  with  the  acids  and  so  hasten 
their  excretion.  The  acids  are  removed  from  the 
blood  and  tissues;  the  dangerous  ketonaemia  is  com- 
batted  while  the  ketonuria  —  namely,  the  elimination 
of  the  acid  products  from  the  blood  —  is  increased. 
At  least,  this  is  what  happens  at  the  commencement  of 
the  alkali  therapy.  Later  the  output  sinks  to  a  lower 
level,  dependent  upon  the  nutritional  intake  and  upon 
the  general  extent  of  the  specific  diabetic  process.  The 
alkali  determines  the  output  of  the  ketone  bodies,  much 
as  large  quantities  of  water  affect  the  urinary  output 
of  the  products  of  the  metabolism  of  albumin. 

The  amounts  of  alkali  required  vary  within  broad 
limits,  from  case  to  case.  When  the  urine  does  not 
give    the    ferric    chloride    reaction,    alkalies    are    not 


NEW   ASPECTS   OF  DIABETES  1 55 

specially  indicated.  In  the  definite  slight  cases  in 
which  the  reaction  appears  when  restricted  diet  is 
taken,  alkalies  are  not  really  necessary,  although  we 
are  accustomed  to  give  5  to  6  grams  daily.  That  this 
quantity  is  sufficient  is  shown  by  the  alkalinity  of  the 
urine.  It  is  only  in  the  medium  cases  of  glycosuria, 
however,  that  the  administration  of  alkalies  is  of  im- 
portance. As  long  as  there  the  ferric  chloride  reaction 
turns  positive  alkalies  should  not  be  foregone.  For 
these  cases,  and  for  all  cases  where  long  periods  of 
alkali  therapy  are  prescribed,  I  do  not  recommend 
more  than  15  to  20  grams  per  day.  There  are  some 
who  advise  the  use  of  large  doses  and  give  40  to  60 
grams  sodium  bicarbonate  daily  for  many  weeks  or 
months.  When  not  a  high  grade  of  acid  intoxication 
threatens,  these  quantities  are  not  necessary;  I  cannot 
rid  myself  of  the  impression  that  such  doses  in  the 
long  run  injure  the  various  functions  of  the  stomach 
and  so  ultimately  disturb  the  entire  general  nutrition. 
One  frequently  finds  that  patients  who  have  taken 
large  quantities  of  alkalies  for  long  periods,  suffer 
from  symptoms  of  hyperacidity.  I  have  given  test 
meals  to  such  diabetic  patients  and  found  the  total 
hydrochloric  acid  values  reach  up  to  0.4  per  cent.  The 
high  alkali  intake  thus  induces  a  compensatory  hy- 
peracidity which,  on  the  one  hand,  opposes  the  object 
of  the  alkali  therapy,  and,  on  the  other  hand,  causes 
discomfort  and  dislocation  of  the  total  energy  ex- 
change. 
If  the  amoiint  is  limited  to  15  grams  daily,  it  is  well 


156      DISORDERS   OF    METABOLISM    AND   NUTRITION 

to  give  5  grams  first  thing  in  the  morning  and  5  grams 
just  before  sleeping  in  a  small  glass  of  plain  or  aerated 
water;  the  remainder  dissolved  in  a  bottle  of  mineral 
water  may  be  administered  during  the  day  as  the 
patient  likes  best,  but  on  no  account  should  it  be  given 
at  meal  times.  Sometimes  it  is  very  useful  to  give 
sodium  citrate  instead  of  the  bicarbonate  citrate. 
The  citrate  is  slightly  laxative  and  this  is  wel- 
come. The  alkali  values  of  the  two  sets  is  about 
equal.  Among  the  other  fixed  alkalies,  there  come 
also  magnesium  and  calcium  in  consideration.  Al- 
though they  are  absorbed  only  incompletely,  they 
are  useful  strings  to  our  bow;  the  magnesium  when 
there  is  a  tendency  to  constipation,  the  carbonate  of 
calcium  when  diarrhoea  occurs.  One  of  the  best  prep- 
arations of  magnesia  is  the  magnesium  perhydrol  of 
Merck ;  it  is  suitable  for  long  continued  use  also. 

The  really  large  doses  of  alkali  are  first  called  for 
when  the  ketonaemia  reaches  a  height  which  is  dan- 
gerous to  life  and  when  we  have  to  face  the  possibility 
of  coma.  This  condition,  of  course,  often  occurs  sud- 
denly ;  but  in  other  instances  it  often  happens  that  for 
several  weeks  it  is  impossible  to  be  sure  whether  coma 
will  or  will  not  set  in.  Sometimes  we  have  a  long  time 
to  battle  with  a  comatoid  stage  in  which  it  is  difficult 
to  prognose  safely  from  hour  to  hour.  Together  with 
general  prostration,  however,  there  is  in  such  cases 
one  s)miptom  which  is  of  prime  importance,  namely,  a 
constipation  due  to  intestinal  paralysis.  Many  years 
*  ago,  the  late  Dr.  Schmitz  of  Neuenahr,  who  made  so 


NEW  ASPECTS  OF  DIABETES  1 57 

many  important  observations  upon  diabetes,  showed 
that  in  those  cases  of  severe  ketonaemia,  it  was  im- 
portant to  evacuate  the  intestinal  contents.  I  must 
acknowledge  the  correctness  of  his  contention,  al- 
though a  theoretical  explanation  is  not  available.  I 
remember  a  case  in  which  the  acetonuria  reached  the 
extraordinary  height  of  7  grams  per  day,  and  in  which 
I  uneasily  awaited  the  onset  of  coma.  The  rectum 
was  distended  with  hard  faeces;  enemata  failed  to 
dislodge  them.  Digital  removal  was  attempted  and 
i  milligram  of  physostigmin  injected.  An  enormous 
stool  resulted,  and  on  the  next  day  the  acetonuria  de- 
creased to  a  fourth  of  its  previous  amount.  In  our 
treatment  of  acidosis  we  must  therefore  take  measures 
for  dealing  also  with  the  constipation. 

With  regard  to  the  administration  of  alkalies,  there 
are  several  means  at  our  disposal.  Via  the  stomach 
hardly  60  grams  a  day  can  be  given.  This  is  not 
sufficient,  as  Magnus  Levy  has  calculated  and  experi- 
ence has  taught  to  neutralize  the  excessive  and  dan- 
gerous grades  of  acidosis.  If  the  colon  is  cleared  out 
it  is  possible  to  utilize  alkaline  enemata  with  good  re- 
sults ;  the  only  useful  form  is  the  so-called  "  drop 
enema  "  composed  of  3  per  cent,  solution  of  sodium 
bicarbonate;  this  will  be  almost  entirely  absorbed, 
while  large  enemata  irritate  the  intestine  so  much, 
that  a  second  enema  will  be  scarcely  retained  or  ab- 
sorbed ;  with  the  "  drop  enema  "  40  to  50  grams  sodium 
bicarbonate  may  be  introduced  and  absorbed  without 
producing  the  slightest  harm  or  irritation. 


158      DISORDERS   OF    METABOLISM    AND   NUTRITION 

In  some  cases  it  is  necessary  to  resort  to  intra- 
venous injections.  Then  it  is  best  to  use  3i  to  4  per 
cent,  sodium  carbonate  solution,  which  contains  double 
the  amount  of  sodium  present  in  the  same  amount 
of  the  bicarbonate.  The  technique  is  the  same  as  that 
for  the  injection  of  salvarsan.  Subcutaneous  injec- 
tions should  be  avoided,  as  local  necrosis  frequently 
follows.  The  blood  is  much  more  tolerant  of  the 
strong  soda  solutions.  The  result  is  sometimes  as- 
tounding. Patients  who  have  been  completely  uncon- 
scious often  after  the  first  300  to  400  c.  c.  of  the  soda 
solution  recover  from  the  coma,  and  after  the  sur- 
mounting of  the  momentary  danger  remain  well  for  a 
relatively  long  period.  Of  course,  these  are  the  rarer 
cases ;  as  a  rule,  the  fatal  issue  is  postponed  for  a  short 
time  only. 

b.  Feeding  (Lceviilose,  Oaten,  Fasting-Day) 

The  question  of  nutriment  during  incipient  coma  is 
an  important  one.  It  is  a  rule  that  carbohydrates 
should  liberally  be  given  and  this  is  mostly  right.  At 
all  events,  I  mean  that  one  cannot  expect  much  from 
carbohydrates  administration  during  the  danger  stages. 
Laevulose  has  been  a  favorite  at  these  times,  because 
it  is  associated  with  a  greater  tendency  to  glycogen 
formation  than  the  other  varieties  of  sugar.  It  is 
not  difficult  to  give  100  grams  or  more  in  the  form 
of  lemonade.  I  have  not  found  the  practical  results 
equal  to  theoretical  expectations.  There  is  little  doubt 
that  Isevulose  cannot  be  relied  upon  in  the  treatment  of 


NEW  ASPECTS  OF  DIABETES  1 59 

diabetes  to  the  extent  its  supporters  have  claimed. 
Although  the  glycosuria  is  less  increased  by  a  single 
dose  of  Isevulose  than  by  such  of  other  sugars,  in 
the  end  laevulose  is  not  less  harmful  than  glucose  or 
saccharose,  etc. 

Besides  laevulose,  milk  and  oat  preparations  are  of 
use  in  the  late  stages  of  acidosis.  Formerly  I  em- 
ployed milk  in  200-250  gram  doses  every  two  hours. 
But  oat  food  proved  to  be  still  better,  and  I  believe 
that  I  am  right  in  saying  that  many  cases  in  which 
coma  threatened  have  been  tided  over  the  crisis  by  an 
exclusive  diet  of  oaten  preparations.  Whichever  form 
of  nutrition  one  chooses  later,  it  seems  to  me  advisable 
at  first  to  take  another  way  of  dietetic  therapy  —  a 
way,  which  at  first  might  cause  hesitation,  but  prac- 
tically gave  the  best  results.  We  give  the  patient  no 
food  at  all  and  only  administer  large  quantities  of 
whiskey  well  diluted.  About  100-150  grams  (3-5 
ozs)  per  day  is  generally  reached.  It  is  astonishing 
how  much  alcohol  these  patients  will  take  without  the 
slightest  after-results,  even  when  it  has  not  been  their 
custom  to  take  alcohol.  On  such  alcohol  days  the 
ketonuria  decreases  to  a  remarkable  degree  and  the 
general  condition  of  the  patient  is  an  agreeable  sur- 
prise. This  is  the  more  remarkable  when  one  con- 
siders that  other  narcotic  poisons,  such  as  chloroform 
and  ether,  increases  the  acidosis.  When,  after  one  or 
two  days  of  alcohol  dietary  an  improvement  appears 
and  the  momentary  danger  is  over,  the  time  has  come 
for  the  use  of  milk  and  oatmeal  soups  and  a  very 


l60      DISORDERS   OF    METABOLISM    AND   NUTRITION 

gradual  and  careful  return  to  the  diet  usually  indicated 
for  diabetics.  Of  course  the  outlook,  sadly  enough, 
is  still  cloudy.  Once  or  twice  we  may  succeed  to 
snatch  from  the  coma  its  victim.  But  as  a  rule,  it  is 
a  matter  of  weeks  or,  at  the  most,  months,  before  a 
further  attack  brings  about  the  end. 

As  a  rule,  it  must  be  considered  that  the  treatment 
of  the  comatose  and  pre-comatose  states  is  a  very  un- 
grateful one ;  hence  so  much  the  more  weight  ought  to 
be  laid  upon  the  precept  that  in  the  early  days  of  the 
diabetic  process  the  end  should  be  sighted  and  by  the 
sparing  of  the  sugar  forming  apparatus  the  tissues 
should  be  enabled  to  retain  the  diastatic  activities  and 
restrain  the  production  of  ketone  bodies.  I  mean,  this 
is  a  thankful  piece  of  work.  The  carrying  out  of  the 
matter  is  rather  difficult,  for  the  diabetic  who  is  not 
the  subject  of  ketonuria  or  other  complications  and 
finds  himself  feeling  in  good  form  is  a  difficult  subject 
to  convince  that  certain  dietetic  restrictions,  ordered 
by  the  physician  who  looks  beyond  the  present  into 
the  future,  are  really  necessary.  We  cannot  hope, 
even  if  we  ensure  the  practical  applications  of  our  ad- 
vice in  the  early  stages,  to  put  an  end  to  diabetic  au- 
tointoxication in  the  world,  for  there  are  many  cases 
which  progress  persistently,  no  matter  what  therapeutic 
measures  we  take.  On  the  other  hand,  however,  there 
are  numerous  other  cases  in  which  success  is  attained 
and  we  are  able  to  hinder,  or  avoid,  the  onset  of  the 
complications  of  coma. 

THE  END 


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